{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:16:11Z","timestamp":1783682171127,"version":"3.55.0"},"reference-count":268,"publisher":"FapUNIFESP (SciELO)","issue":"suppl 2","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["309994\/2023-3"],"award-info":[{"award-number":["309994\/2023-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["446909\/2024-6"],"award-info":[{"award-number":["446909\/2024-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["RED-00110-23"],"award-info":[{"award-number":["RED-00110-23"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["APD-01401-25"],"award-info":[{"award-number":["APD-01401-25"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FIOCRUZ","award":["309994\/2023-3"],"award-info":[{"award-number":["309994\/2023-3"]}]},{"name":"FIOCRUZ","award":["446909\/2024-6"],"award-info":[{"award-number":["446909\/2024-6"]}]},{"name":"FIOCRUZ","award":["RED-00110-23"],"award-info":[{"award-number":["RED-00110-23"]}]},{"name":"FIOCRUZ","award":["APD-01401-25"],"award-info":[{"award-number":["APD-01401-25"]}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"crossref","award":["309994\/2023-3"],"award-info":[{"award-number":["309994\/2023-3"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"crossref","award":["446909\/2024-6"],"award-info":[{"award-number":["446909\/2024-6"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"crossref","award":["RED-00110-23"],"award-info":[{"award-number":["RED-00110-23"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"crossref","award":["APD-01401-25"],"award-info":[{"award-number":["APD-01401-25"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mem. Inst. Oswaldo Cruz"],"abstract":"<jats:p>The treatment of Chagas disease (CD) has relied for more than five decades on two drugs, benznidazole (BZ) and nifurtimox (NTX), both with significant limitations and severe adverse effects. Their limited efficacy during the chronic phase underscores the urgent need for new chemotherapeutic strategies. The pursuit of new therapeutic agents for CD is focused on identifying molecular targets essential for Trypanosoma cruzi survival that are either absent or highly divergent in human, thereby enhancing selectivity and minimising off-target toxicity. These targets exploit the parasite's unique biology at multiple levels. Key metabolic vulnerabilities include: ergosterol biosynthesis, a sterol pathway distinct from human cholesterol metabolism; glycosomal metabolism, reflecting parasite\u00b4s unique compartmentalisation of glycolysis; and redox homeostasis, which depends on trypanothione rather than glutathione. Additional promising avenues involve the parasite's genetic and epigenetic regulation, mRNA processing and translational control. Furthermore, virulence-associated factors, and specific enzymes such as type I nitroreductase (NTR-1) can be exploited for selective prodrug activation. The complex genomic organisation and pronounced plasticity of T. cruzi complicate the identification of novel therapeutic targets. The abundance of proteins annotated as hypothetical or of unknown function further obscure critical metabolic pathways that could serve as druggable targets. In this context, the discovery of new drugs for CD strategically integrates phenotypic, target-based, and computational approaches, all of which require rigorous validation through preclinical in vitro and in vivo studies. Although modern approaches have yielded several promising lead compounds, successfully controlling CD will also depend on overcoming socioeconomic and access-related barriers to ensure that new therapies reach the populations most affected by this neglected tropical disease.<\/jats:p>","DOI":"10.1590\/0074-02760250299","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T10:43:53Z","timestamp":1783680233000},"source":"Crossref","is-referenced-by-count":0,"title":["Advances and challenges in the search for new treatments for Chagas disease"],"prefix":"10.1590","volume":"121","author":[{"given":"Ana Maria Murta","family":"Santi","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi Alvarenga","family":"Lima","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-2155","authenticated-orcid":false,"given":"Silvane Maria Fonseca","family":"Murta","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2026]]},"reference":[{"key":"ref1","series-title":"Chagas disease (also known as American trypanosomiasis)","year":"2025"},{"issue":"1","key":"ref2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4269\/ajtmh.14-0826","article-title":"Access to care for Chagas disease in the United States: a health systems analysis","volume":"93","author":"Manne-Goehler J","year":"2015","journal-title":"Am Soc Trop Med Hyg"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00436-016-5291-z","article-title":"Overcoming research barriers in Chagas disease \u2014 designing effective implementation science","volume":"116","author":"Henao-Mart\u00ednez AF","year":"2017","journal-title":"Parasitol Res"},{"key":"ref4","first-page":"1","article-title":"Estimaci\u00f3n de la demanda de medicamentos antichag\u00e1sicos: una contribuci\u00f3n para el acceso en Am\u00e9rica Latina","volume":"41","author":"Chaves GC","year":"2017","journal-title":"Rev Panam Salud Publica"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5334\/gh.484","article-title":"WHF IASC roadmap on Chagas disease","volume":"15","author":"Echeverr\u00eda LE","year":"2020","journal-title":"Glob Heart"},{"key":"ref6","series-title":"Less than 10% of people with Chagas receive a diagnosis. PAHO\/WHO","year":"2023"},{"key":"ref7","article-title":"Chagas disease in Brazil: new challenges and perspectives for old problems","volume":"120","author":"Santos FLN","year":"2025","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"2","key":"ref8","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ijcard.2010.02.036","article-title":"Chagas disease and mortality in old age as an emerging issue: 10 year follow-up of the Bambu\u00ed population-based cohort study (Brazil)","volume":"145","author":"Lima-Costa MF","year":"2010","journal-title":"Int J Cardiol"},{"key":"ref9","article-title":"The health-related quality of life in patients with Chagas disease: the state of the art","volume":"55","author":"Almeida ILGID","year":"2022","journal-title":"Rev Soc Bras Med Trop"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010850","article-title":"Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation","volume":"17","author":"Altcheh J","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006814","article-title":"Beneficial effects of benznidazole in Chagas disease: NIH SaMi-Trop cohort study","volume":"12","author":"Cardoso CS","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"100694","DOI":"10.1016\/j.eclinm.2020.100694","article-title":"Benznidazole decreases the risk of chronic Chagas disease progression and cardiovascular events: a long-term follow up study","volume":"31","author":"Hasslocher-Moreno AM","year":"2021","journal-title":"EClinicalMedicine"},{"issue":"10","key":"ref13","doi-asserted-by":"crossref","first-page":"724","DOI":"10.7326\/0003-4819-144-10-200605160-00006","article-title":"Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial","volume":"144","author":"Viotti R","year":"2006","journal-title":"Ann Intern Med"},{"key":"ref14","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760240229","article-title":"Parasitological cure and clinical benefits of benznidazole treatment in patients from the Jequitinhonha Valley, MG, Brazil, with recent chronic infection by Trypanosoma cruzi II","volume":"120","author":"de Lana M","year":"2025","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijid.2018.11.369","article-title":"Elevated IL-17 levels and echocardiographic signs of preserved myocardial function in benznidazole-treated individuals with chronic Chagas' disease","volume":"79","author":"Camara EJN","year":"2019","journal-title":"Int J Infect Dis"},{"issue":"12","key":"ref16","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1111\/bcp.16214","article-title":"Adverse events associated with benznidazole treatment for Chagas disease in children and adults","volume":"90","author":"Cruz CV","year":"2024","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"ref17","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s11886-024-02113-7","article-title":"Chagas disease: epidemiology, diagnosis, and treatment","volume":"26","author":"Swett MC","year":"2024","journal-title":"Curr Cardiol Rep"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003493","article-title":"Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line","volume":"9","author":"Alonso-Padilla J","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"ref19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003259","article-title":"High throughput screening for anti-Trypanosoma cruzi drug discovery","volume":"8","author":"Alonso-Padilla J","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref20","first-page":"1","article-title":"State-of-the-art in the drug discovery pathway for Chagas disease: a framework for drug development and target validation","volume":"14","author":"Gabald\u00f3n-Figueira JC","year":"2023","journal-title":"Res Rep Trop Med"},{"issue":"7","key":"ref21","article-title":"In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds","volume":"4","author":"Canavaci AMC","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/17460441.2024.2349155","article-title":"New drug discovery strategies for the treatment of benznidazole-resistance in Trypanosoma cruzi, the causative agent of Chagas disease","volume":"19","author":"Murta SMF","year":"2024","journal-title":"Expert Opin Drug Discov"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1591148","DOI":"10.3389\/fmed.2025.1591148","article-title":"Reporter genes and transgenic Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae): applications for screening new drugs against Chagas disease","volume":"12","author":"Oliveira DSDS","year":"2025","journal-title":"Front Med"},{"key":"ref24","article-title":"Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models","volume":"119","author":"Soeiro MNC","year":"2024","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijpddr.2012.01.003","article-title":"Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it?","volume":"2","author":"Freitas-Junior LH","year":"2012","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ref26","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760200501","article-title":"The translational challenge in Chagas disease drug development","volume":"117","author":"Kratz JM","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41579-022-00777-y","article-title":"Anti-trypanosomatid drug discovery: progress and challenges","volume":"21","author":"De Rycker M","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/17460441.2018.1417380","article-title":"Phenotypic screening approaches for Chagas disease drug discovery","volume":"13","author":"Chatelain E","year":"2018","journal-title":"Expert Opin Drug Discov"},{"issue":"7619","key":"ref29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nature19339","article-title":"Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness","volume":"537","author":"Khare S","year":"2016","journal-title":"Nature"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1080\/14728222.2023.2264512","article-title":"Molecular targets for Chagas disease: validation, challenges and lead compounds for widely exploited targets","volume":"27","author":"De Souza ML","year":"2023","journal-title":"Expert Opin Ther Targets"},{"issue":"6","key":"ref31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s00436-024-08257-3","article-title":"Listen to what the animals say: a systematic review and meta-analysis of sterol 14-demethylase inhibitor efficacy for in vivo models of Trypanosoma cruzi infection","volume":"123","author":"Bisio MMC","year":"2024","journal-title":"Parasitol Res"},{"issue":"22","key":"ref32","doi-asserted-by":"crossref","first-page":"8809","DOI":"10.3390\/ijms21228809","article-title":"Repositioned drugs for Chagas disease unveiled via structure-based drug repositioning","volume":"21","author":"Adasme MF","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref33","article-title":"Molecular docking and quantitative structure-activity relationships for a series of Trypanosoma cruzi dihydroorotate dehydrogenase inhibitors","volume":"61","author":"Jesus GCD","year":"2025","journal-title":"Braz J Pharm Sci"},{"key":"ref34","article-title":"Drug repurposing for trypanosomiasis: using machine learning models and polypharmacology to identify multitarget candidates","author":"Domingues KZA","year":"2025","journal-title":"J Braz Chem Soc"},{"issue":"22","key":"ref35","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.3390\/molecules25225483","article-title":"Chagas disease: perspectives on the past and present and challenges in drug discovery","volume":"25","author":"Mansoldo FRP","year":"2020","journal-title":"Molecules"},{"issue":"6","key":"ref36","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1021\/pr700659m","article-title":"Proteomic analysis of Trypanosoma cruzi resistance to benznidazole","volume":"7","author":"Andrade HM","year":"2008","journal-title":"J Proteome Res"},{"issue":"9","key":"ref37","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11306-019-1583-5","article-title":"Metabolomics, lipidomics and proteomics profiling of myoblasts infected with Trypanosoma cruzi after treatment with different drugs against Chagas disease","volume":"15","author":"Hennig K","year":"2019","journal-title":"Metabolomics"},{"issue":"5","key":"ref38","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002844","article-title":"Benznidazole Biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics","volume":"8","author":"Trochine A","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0314189","article-title":"Transcriptomic analysis of benznidazole-resistant Trypanosoma cruzi clone reveals nitroreductase I-independent resistance mechanisms","volume":"20","author":"Mej\u00eda-Jaramillo AM","year":"2025","journal-title":"PLoS One"},{"issue":"7","key":"ref40","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1002\/jcb.25978","article-title":"Transcriptome and functional genomics reveal the participation of adenine phosphoribosyltransferase in Trypanosoma cruzi resistance to benznidazole","volume":"118","author":"Garc\u00eda-Huertas P","year":"2017","journal-title":"J Cell Biochem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fcimb.2020.00005","article-title":"The influence of recombinational processes to induce dormancy in Trypanosoma cruzi","volume":"10","author":"Resende BC","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"ref42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13071-023-05775-4","article-title":"Transcriptomic analysis of benznidazole-resistant and susceptible Trypanosoma cruzi populations","volume":"16","author":"Lima DA","year":"2023","journal-title":"Parasit Vectors"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006388","article-title":"Expanding the toolbox for Trypanosoma cruzi: a parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR\/Cas9 functionality for rapid in vivo localisation and phenotyping","volume":"12","author":"Costa FC","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"issue":"49","key":"ref44","doi-asserted-by":"crossref","first-page":"25505","DOI":"10.1074\/jbc.M116.749655","article-title":"CRISPR\/Cas9-mediated endogenous C-terminal Tagging of Trypanosoma cruzi genes reveals the acidocalcisome localization of the inositol 1,4,5-trisphosphate receptor","volume":"291","author":"Lander N","year":"2016","journal-title":"J Biol Chem"},{"key":"ref45","article-title":"Antioxidant defence system as a rational target for Chagas disease and Leishmaniasis chemotherapy","volume":"117","author":"Santi AMM","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1590\/S0074-02762010000200022","article-title":"In vitro and in vivo experimental models for drug screening and development for Chagas disease","volume":"105","author":"Romanha AJ","year":"2010","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.3390\/molecules25122799","article-title":"Challenges in Chagas disease drug development","volume":"25","author":"Francisco AF","year":"2020","journal-title":"Molecules"},{"issue":"11","key":"ref48","doi-asserted-by":"crossref","first-page":"5821","DOI":"10.1128\/AAC.01227-12","article-title":"Targeting the substrate preference of a type I nitroreductase to develop antitrypanosomal quinone-based prodrugs","volume":"56","author":"Hall BS","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ref49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/AAC.05135-11","article-title":"Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation","volume":"56","author":"Hall BS","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"ref50","doi-asserted-by":"crossref","DOI":"10.1017\/S1462399409001252","article-title":"Trypanocidal drugs: mechanisms, resistance and new targets","volume":"11","author":"Wilkinson SR","year":"2009","journal-title":"Expert Rev Mol Med"},{"key":"ref51","doi-asserted-by":"crossref","DOI":"10.1590\/s1678-9946202062052","article-title":"Ideal benznidazole dose regimen in chronic chagasic patients: a systematic review","volume":"62","author":"Frade VP","year":"2020","journal-title":"Rev Inst Med Trop S\u00e3o Paulo"},{"key":"ref52","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760240177","article-title":"Pharmacokinetics of two pharmaceutical presentations of benznidazole in adult Trypanosoma cruzi infected population","volume":"120","author":"Hern\u00e1ndez Y","year":"2025","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"4","key":"ref53","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01912-16","article-title":"Pharmacokinetics of benznidazole in healthy volunteers and implications in future clinical trials","volume":"61","author":"Molina I","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"107834","DOI":"10.1016\/j.exppara.2020.107834","article-title":"Low-dose of benznidazole promotes therapeutic cure in experimental chronic Chagas' disease with absence of parasitism in blood, heart and colon","volume":"210","author":"Perin L","year":"2020","journal-title":"Exp Parasitol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"107264","DOI":"10.1016\/j.actatropica.2024.107264","article-title":"Tackling the challenges of human Chagas disease: a comprehensive review of treatment strategies in the chronic phase and emerging therapeutic approaches","volume":"256","author":"Ramos LG","year":"2024","journal-title":"Acta Trop"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"409","DOI":"10.2147\/JEP.S267378","article-title":"Review on experimental treatment strategies against Trypanosoma cruzi","volume":"13","author":"Mazzeti AL","year":"2021","journal-title":"J Exp Pharmacol"},{"issue":"Suppl. 1","key":"ref57","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1590\/S0074-02761999000700024","article-title":"Characterization of Trypanosoma cruzi","volume":"94","author":"Murta SMF","year":"1999","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"102615","DOI":"10.1016\/j.mib.2025.102615","article-title":"The importance of persistence and dormancy in Trypanosoma cruzi infection and Chagas disease","volume":"86","author":"Bunkofske ME","year":"2025","journal-title":"Curr Opin Microbiol"},{"issue":"20","key":"ref59","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202400293","article-title":"Structure-metabolism relationships of benzimidazole derivatives with anti-Trypanosoma cruzi activity for Chagas disease","volume":"19","author":"Espinoza-Ch\u00e1vez RM","year":"2024","journal-title":"ChemMedChem"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"112047","DOI":"10.1016\/j.jinorgbio.2022.112047","article-title":"Silver and copper-benznidazole derivatives as potential antiparasitic metallodrugs: synthesis, characterization, and biological evaluation","volume":"239","author":"De Souza CC","year":"2023","journal-title":"J Inorg Biochem"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"107993","DOI":"10.1016\/j.bioorg.2024.107993","article-title":"Discovery of a new eugenol-benznidazole hybrid active against different evolutive stages of Trypanosoma cruzi","volume":"154","author":"De Melo IM","year":"2025","journal-title":"Bioorganic Chem"},{"issue":"7","key":"ref62","article-title":"New 2-nitroimidazole-N-acylhydrazones, analogs of benznidazole, as anti-Trypanosoma cruzi agents","volume":"357","author":"Pitombeira MCSR","year":"2024","journal-title":"Arch Pharm (Weinheim)"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"115451","DOI":"10.1016\/j.ejmech.2023.115451","article-title":"Design, synthesis and antitrypanosomatid activity of 2-nitroimidazole-3,5-disubstituted isoxazole compounds based on benznidazole","volume":"260","author":"Carvalho DB","year":"2023","journal-title":"Eur J Med Chem"},{"issue":"1","key":"ref64","doi-asserted-by":"crossref","first-page":"103084","DOI":"10.1016\/j.arcmed.2024.103084","article-title":"New drugs and promising drug combinations in the treatment of Chagas disease in Brazil: a systematic review and meta-analysis","volume":"56","author":"Freire ES","year":"2025","journal-title":"Arch Med Res"},{"issue":"11","key":"ref65","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1017\/S0031182021001001","article-title":"Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment","volume":"148","author":"Mazzeti AL","year":"2021","journal-title":"Parasitology"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"7820890","DOI":"10.1155\/2018\/7820890","article-title":"Atorvastatin downregulates in vitro methyl methanesulfonate and cyclophosphamide alkylation-mediated cellular and DNA injuries","volume":"2018","author":"Araujo-Lima CF","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"926699","DOI":"10.3389\/fcimb.2022.926699","article-title":"The repositioned drugs disulfiram\/diethyldithiocarbamate combined to benznidazole: searching for Chagas disease selective therapy, preventing toxicity and drug resistance","volume":"12","author":"Almeida-Silva J","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"7","key":"ref68","article-title":"Disulfiram repurposing in the combined chemotherapy of Chagas disease: a protocol for phase I\/II clinical trial","volume":"2","author":"Saraiva RM","year":"2021","journal-title":"Med Case Rep Study Protoc"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"855119","DOI":"10.3389\/fcimb.2022.855119","article-title":"Miltefosine and benznidazole combination improve anti-Trypanosoma cruzi in vitro and in vivo efficacy","volume":"12","author":"Gulin JEN","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"11","key":"ref70","doi-asserted-by":"crossref","DOI":"10.1128\/aac.00284-22","article-title":"Drug repurposing in Chagas disease: chloroquine potentiates benznidazole activity against Trypanosoma cruzi in vitro and in vivo","volume":"66","author":"Pandey RP","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jgar.2021.10.030","article-title":"Prodrugs as new therapies against Chagas disease: in vivo synergy between Trypanosoma cruzi proline racemase inhibitors and benznidazole","volume":"28","author":"De Melo GD","year":"2022","journal-title":"J Glob Antimicrob Resist"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"106314","DOI":"10.1016\/j.actatropica.2022.106314","article-title":"4-nitrobenzoylcoumarin potentiates the antiparasitic, anti-inflammatory and cardioprotective effects of benznidazole in a murine model of acute Trypanosoma cruzi infection","volume":"228","author":"Vilas-Boas DF","year":"2022","journal-title":"Acta Trop"},{"issue":"726","key":"ref73","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adg8105","article-title":"Short-course combination treatment for experimental chronic Chagas disease","volume":"15","author":"Gonz\u00e1lez S","year":"2023","journal-title":"Sci Transl Med"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"154788","DOI":"10.1016\/j.phymed.2023.154788","article-title":"Candimine from Hippeastrum escoipense (Amaryllidaceae): anti-Trypanosoma cruzi activity and synergistic effect with benznidazole","volume":"114","author":"Ortiz JE","year":"2023","journal-title":"Phytomedicine"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"116742","DOI":"10.1016\/j.biopha.2024.116742","article-title":"Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection","volume":"175","author":"Barbosa JMC","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"ref76","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00876-17","article-title":"Vaccine-linked chemotherapy improves benznidazole efficacy for acute Chagas disease","volume":"86","author":"Jones K","year":"2018","journal-title":"Infect Immun"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"106334","DOI":"10.1016\/j.actatropica.2022.106334","article-title":"Assessment of a combined treatment with a therapeutic vaccine and benznidazole for the Trypanosoma cruzi chronic infection","volume":"229","author":"Prochetto E","year":"2022","journal-title":"Acta Trop"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jconrel.2021.09.020","article-title":"Road map to the treatment of neglected tropical diseases: Nanocarriers interventions","volume":"339","author":"Joshi G","year":"2021","journal-title":"J Controlled Release"},{"issue":"18","key":"ref79","doi-asserted-by":"crossref","first-page":"13778","DOI":"10.3390\/ijms241813778","article-title":"From benznidazole to new drugs: nanotechnology contribution in Chagas disease","volume":"24","author":"Gomes DC","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"2","key":"ref80","doi-asserted-by":"crossref","first-page":"140577","DOI":"10.1016\/j.bbapap.2020.140577","article-title":"Update on relevant trypanosome peptidases: validated targets and future challenges","volume":"1869","author":"Alvarez VE","year":"2021","journal-title":"Biochim Biophys Acta Proteins Proteomics"},{"issue":"15","key":"ref81","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.2174\/09298673113209990139","article-title":"Glycosomal targets for anti-trypanosomatid drug discovery","volume":"21","author":"Barros-Alvarez X","year":"2014","journal-title":"Curr Med Chem"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"112020","DOI":"10.1016\/j.biopha.2021.112020","article-title":"Advances in the treatment of Chagas disease: promising new drugs, plants and targets","volume":"142","author":"Garc\u00eda-Huertas P","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/B978-0-12-385863-4.00004-6","article-title":"Targeting Trypanosoma cruzi sterol 14\u03b1-demethylase (CYP51)","volume":"75","author":"Lepesheva GI","year":"2011","journal-title":"Adv Parasitol"},{"issue":"9","key":"ref84","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1128\/AAC.00070-13","article-title":"In vitro and in vivo studies of the antiparasitic activity of sterol 14\u03b1-Demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi","volume":"57","author":"Soeiro MNC","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"ref85","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1021\/acsinfecdis.8b00253","article-title":"Successful aspects of the coadministration of sterol 14\u03b1-Demethylase inhibitor VFV and benznidazole in experimental mouse models of Chagas disease caused by the drug-resistant strain of Trypanosoma cruzi","volume":"5","author":"Guedes-da-Silva FH","year":"2019","journal-title":"ACS Infect Dis"},{"issue":"20","key":"ref86","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1056\/NEJMoa1313122","article-title":"Randomized trial of posaconazole and benznidazole for chronic Chagas' disease","volume":"370","author":"Molina I","year":"2014","journal-title":"N Engl J Med"},{"issue":"4","key":"ref87","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S1473-3099(17)30538-8","article-title":"Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial","volume":"18","author":"Torrico F","year":"2018","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"ref88","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1128\/AAC.00520-15","article-title":"Limited ability of posaconazole to cure both acute and chronic Trypanosoma cruzi infections revealed by highly sensitive in vivo imaging","volume":"59","author":"Francisco AF","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"ref89","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006612","article-title":"Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas' disease drug discovery","volume":"12","author":"MacLean LM","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"issue":"21","key":"ref90","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1016\/j.febslet.2014.08.030","article-title":"Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition","volume":"588","author":"Cherkesova TS","year":"2014","journal-title":"FEBS Lett"},{"issue":"6","key":"ref91","doi-asserted-by":"crossref","first-page":"919","DOI":"10.3390\/ph18060919","article-title":"TrypPROTACs unlocking new therapeutic strategies for Chagas disease","volume":"18","author":"Rodriguez Gini AL","year":"2025","journal-title":"Pharmaceuticals"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fchem.2018.00088","article-title":"Targeting channels and transporters in protozoan parasite infections","volume":"6","author":"Meier A","year":"2018","journal-title":"Front Chem"},{"key":"ref93","article-title":"Thiol efflux mediated by an ABCC-like transporter participates for Trypanosoma cruzi adaptation to environmental and chemotherapeutic stresses","author":"Da Costa KM","year":"2020","journal-title":"bioRxiv [Preprint]"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"105161","DOI":"10.1016\/j.actatropica.2019.105161","article-title":"Mapping benznidazole resistance in trypanosomatids and exploring evolutionary histories of nitroreductases and ABCG transporter protein sequences","volume":"200","author":"Petravicius PO","year":"2019","journal-title":"Acta Trop"},{"issue":"9","key":"ref95","article-title":"Glycosomal ABC transporter 3 (GAT3) deletion enhances the oxidative stress responses and reduces the infectivity of Trypanosoma cruzi","volume":"19","author":"Lima DA","year":"2025","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ref96","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00377-17","article-title":"An intracellular ammonium transporter is necessary for replication, differentiation, and resistance to starvation and osmotic stress in Trypanosoma cruzi","volume":"3","author":"Cruz-Bustos T","year":"2018","journal-title":"mSphere"},{"key":"ref97","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760240183","article-title":"Looking for approved-medicines to be repositioned as anti-Trypanosoma cruzi agents. Identification of new chemotypes with good individual- or in combination-biological behaviours","volume":"120","author":"Veira C","year":"2025","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"6","key":"ref98","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1021\/acsinfecdis.5c00094","article-title":"Anti-parasitics with a triple threat: targeting parasite enzymes, the proton motive force, and host cell-mediated killing","volume":"11","author":"Pandey AM","year":"2025","journal-title":"ACS Infect Dis"},{"issue":"3","key":"ref99","doi-asserted-by":"crossref","first-page":"107092","DOI":"10.1016\/j.ijantimicag.2024.107092","article-title":"A yeast-based high-throughput screen identifies inhibitors of trypanosomatid HRG heme transporters with potent leishmanicidal and trypanocidal activity","volume":"63","author":"Cabello-Donayre M","year":"2024","journal-title":"Int J Antimicrob Agents"},{"key":"ref100","article-title":"Transcriptomic response to different heme sources in Trypanosoma cruzi","author":"Tevere E","year":"2025","journal-title":"BioRxiv Prepr Serv Biol [Preprint]"},{"issue":"4","key":"ref101","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1590\/S0001-37652007000400007","article-title":"The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease","volume":"79","author":"Igoillo-Esteve M","year":"2007","journal-title":"An Acad Bras Ci\u00eanc"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"135510","DOI":"10.1016\/j.ijbiomac.2024.135510","article-title":"Structural dynamics of the TPR domain of the peroxisomal cargo receptor Pex5 in Trypanosoma","volume":"280","author":"Banasik M","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.molbiopara.2019.02.008","article-title":"Proteomic analysis of glycosomes from Trypanosoma cruzi epimastigotes","volume":"229","author":"Acosta H","year":"2019","journal-title":"Mol Biochem Parasitol"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1042\/bse0510015","article-title":"Glucose metabolism in Trypanosoma cruzi","volume":"51","author":"Maugeri DA","year":"2011","journal-title":"Essays Biochem"},{"issue":"8","key":"ref105","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.3390\/ijms25084319","article-title":"Discovery of strong 3-Nitro-2-Phenyl-2H-Chromene analogues as antitrypanosomal agents and inhibitors of Trypanosoma cruzi glucokinase","volume":"25","author":"Carey SM","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.biochi.2023.09.014","article-title":"At the outer part of the active site in Trypanosoma cruzi glucokinase: the role of phenylalanine 337","volume":"218","author":"Carey SM","year":"2024","journal-title":"Biochimie"},{"issue":"1","key":"ref107","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1021\/ml400259d","article-title":"Identification of ML251, a potent inhibitor of T. brucei and T. cruzi phosphofructokinase","volume":"5","author":"Brimacombe KR","year":"2014","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"ref108","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/s41467-021-21273-6","article-title":"Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice","volume":"12","author":"McNae IW","year":"2021","journal-title":"Nat Commun"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"1129791","DOI":"10.3389\/fcimb.2023.1129791","article-title":"Metabolic insights into phosphofructokinase inhibition in bloodstream-form trypanosomes","volume":"13","author":"Nare Z","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"116577","DOI":"10.1016\/j.bmc.2021.116577","article-title":"Examination of multiple Trypanosoma cruzi targets in a new drug discovery approach for Chagas disease","volume":"58","author":"Beltran-Hortelano I","year":"2022","journal-title":"Bioorg Med Chem"},{"issue":"3","key":"ref111","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0014-5793(98)00154-9","article-title":"Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design","volume":"424","author":"Souza DHF","year":"1998","journal-title":"FEBS Lett"},{"issue":"19","key":"ref112","doi-asserted-by":"crossref","first-page":"8889","DOI":"10.1016\/j.bmc.2008.08.057","article-title":"Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi","volume":"16","author":"Pereira JM","year":"2008","journal-title":"Bioorg Med Chem"},{"issue":"2","key":"ref113","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1476-5381.2009.00524.x","article-title":"Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro \/ in vivo trypanocidal activity","volume":"160","author":"Silva JJN","year":"2010","journal-title":"Br J Pharmacol"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"127723","DOI":"10.1016\/j.bmcl.2020.127723","article-title":"Design, synthesis, and evaluation of substrate - analogue inhibitors of Trypanosoma cruzi ribose 5-phosphate isomerase type B","volume":"32","author":"Gonzalez SN","year":"2021","journal-title":"Bioorg Med Chem Lett"},{"issue":"13","key":"ref115","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1021\/jm031066i","article-title":"Selective Inhibition of Trypanosoma brucei 6-phosphogluconate dehydrogenase by high-energy intermediate and transition-state analogues","volume":"47","author":"Dardonville C","year":"2004","journal-title":"J Med Chem"},{"key":"ref116","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760210379","article-title":"Is the mitochondrion a promising drug target in trypanosomatids?","volume":"117","author":"Pedra-Rezende Y","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"1","key":"ref117","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3390\/pathogens14010073","article-title":"Mitochondrial DNA structure in Trypanosoma cruzi","volume":"14","author":"Herreros-Cabello A","year":"2025","journal-title":"Pathogens"},{"issue":"7","key":"ref118","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005058","article-title":"Utilizing chemical genomics to identify cytochrome b as a novel drug target for Chagas Disease","volume":"11","author":"Khare S","year":"2015","journal-title":"PLoS Pathog"},{"issue":"6","key":"ref119","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1021\/acs.jmedchem.9b01852","article-title":"Discovery and optimization of a compound series active against Trypanosoma cruzi, the causative agent of Chagas disease","volume":"63","author":"Harrison JR","year":"2020","journal-title":"J Med Chem"},{"issue":"3","key":"ref120","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1021\/acsinfecdis.9b00426","article-title":"The Qi site of cytochrome b is a promiscuous drug target in Trypanosoma cruzi and Leishmania donovani","volume":"6","author":"Wall RJ","year":"2020","journal-title":"ACS Infect Dis"},{"issue":"20","key":"ref121","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/cmdc.201800500","article-title":"Folates in Trypanosoma brucei: achievements and opportunities","volume":"13","author":"Cullia G","year":"2018","journal-title":"ChemMedChem"},{"issue":"12","key":"ref122","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1016\/j.bbagen.2017.09.012","article-title":"Comparative mapping of on-targets and off-targets for the discovery of anti-trypanosomatid folate pathway inhibitors","volume":"1861","author":"Panecka-Hofman J","year":"2017","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"2-3","key":"ref123","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0925-4439(02)00088-1","article-title":"Inhibitors of dihydrofolate reductase in leishmania and trypanosomes","volume":"1587","author":"Gilbert IH","year":"2002","journal-title":"Biochim Biophys Acta"},{"issue":"12","key":"ref124","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001418","article-title":"Knockout of the dhfr-ts Gene in Trypanosoma cruzi generates attenuated parasites able to confer protection against a virulent challenge","volume":"5","author":"Perez Brandan C","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"issue":"9","key":"ref125","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1080\/17460441.2022.2113776","article-title":"Anti-trypanosomatid structure-based drug design - lessons learned from targeting the folate pathway","volume":"17","author":"Panecka-Hofman J","year":"2022","journal-title":"Expert Opin Drug Discov"},{"key":"ref126","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/B978-0-7020-4087-0.00055-3","article-title":"Disorders of purines and pyrimidines","volume":"120","author":"Kelley R","year":"2014","journal-title":"Handb Clin Neurol"},{"issue":"1","key":"ref127","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.parint.2005.08.001","article-title":"Genetic diversity and kinetic properties of Trypanosoma cruzi dihydroorotate dehydrogenase isoforms","volume":"55","author":"Sariego I","year":"2006","journal-title":"Parasitol Int"},{"issue":"1","key":"ref128","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00239-004-0078-8","article-title":"The origin of dihydroorotate dehydrogenase genes of kinetoplastids, with special reference to their biological significance and adaptation to anaerobic, parasitic conditions","volume":"60","author":"Annoura T","year":"2005","journal-title":"J Mol Evol"},{"issue":"12","key":"ref129","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1016\/j.ejmech.2010.09.055","article-title":"Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery","volume":"45","author":"Cheleski J","year":"2010","journal-title":"Eur J Med Chem"},{"issue":"41","key":"ref130","doi-asserted-by":"crossref","first-page":"10881","DOI":"10.1021\/bi800413r","article-title":"Structures of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with substrates and products: atomic resolution insights into mechanisms of dihydroorotate oxidation and fumarate reduction","volume":"47","author":"Inaoka DK","year":"2008","journal-title":"Biochemistry"},{"issue":"5","key":"ref131","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0125829","article-title":"Pharmacophore modeling for anti-Chagas drug design using the fragment molecular orbital method","volume":"10","author":"Yoshino R","year":"2015","journal-title":"PLoS One"},{"issue":"19","key":"ref132","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1021\/acs.biochem.2c00312","article-title":"Kinetic characterization and inhibition of Trypanosoma cruzi hypoxanthine-guanine phosphoribosyltransferases","volume":"61","author":"Glockzin K","year":"2022","journal-title":"Biochemistry"},{"issue":"6","key":"ref133","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02264-18","article-title":"Synergic effect of allopurinol in combination with nitroheterocyclic compounds against Trypanosoma cruzi","volume":"63","author":"Mazzeti AL","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"ref134","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1128\/AAC.25.2.292","article-title":"Biological action of inosine analogs in Leishmania and Trypanosoma spp.","volume":"25","author":"Marr JJ","year":"1984","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ref135","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/AAC.27.4.491","article-title":"In vitro and in vivo activities of formycin B against Trypanosoma cruzi","volume":"27","author":"McCabe RE","year":"1985","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"ref136","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1021\/acs.jmedchem.1c00135","article-title":"Revisiting Pyrazolo[3,4-d]pyrimidine Nucleosides as Anti-Trypanosoma cruzi and antileishmanial agents","volume":"64","author":"Bouton J","year":"2021","journal-title":"J Med Chem"},{"issue":"20","key":"ref137","doi-asserted-by":"crossref","first-page":"9287","DOI":"10.1021\/acs.jmedchem.8b00999","article-title":"Discovery of Novel 7-Aryl 7-Deazapurine 3\u2032-Deoxy-ribofuranosyl nucleosides with potent activity against Trypanosoma cruzi","volume":"61","author":"Hulpia F","year":"2018","journal-title":"J Med Chem"},{"issue":"12","key":"ref138","doi-asserted-by":"crossref","first-page":"6729","DOI":"10.1021\/cr9002165","article-title":"C-Nucleosides: synthetic strategies and biological applications","volume":"109","author":"Hocek M","year":"2009","journal-title":"Chem Rev"},{"issue":"6","key":"ref139","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1021\/ml500077j","article-title":"Discovery and synthesis of C-nucleosides as potential new anti-HCV agents","volume":"5","author":"Draffan AG","year":"2014","journal-title":"ACS Med Chem Lett"},{"key":"ref140","doi-asserted-by":"crossref","first-page":"113101","DOI":"10.1016\/j.ejmech.2020.113101","article-title":"Synthesis and evaluation of a collection of purine-like C-nucleosides as antikinetoplastid agents","volume":"212","author":"Bouton J","year":"2021","journal-title":"Eur J Med Chem"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"114165","DOI":"10.1016\/j.ejmech.2022.114165","article-title":"N-modification of 7-Deazapurine nucleoside analogues as Anti-Trypanosoma cruzi and anti-Leishmania agents: structure-activity relationship exploration and in vivo evaluation","volume":"231","author":"Lin C","year":"2022","journal-title":"Eur J Med Chem"},{"issue":"22","key":"ref142","doi-asserted-by":"crossref","first-page":"5234","DOI":"10.3390\/molecules29225234","article-title":"Nucleoside analogues for Chagas disease and leishmaniasis therapy: current status and future perspectives","volume":"29","author":"Nwoke EA","year":"2024","journal-title":"Molecules"},{"issue":"11","key":"ref143","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.bbagen.2008.03.006","article-title":"Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism","volume":"1780","author":"Krauth-Siegel RL","year":"2008","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"7","key":"ref144","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1042\/BCJ20170698","article-title":"Cardiomyocyte diffusible redox mediators control Trypanosoma cruzi infection: role of parasite mitochondrial iron superoxide dismutase","volume":"475","author":"Estrada D","year":"2018","journal-title":"Biochem J"},{"issue":"17","key":"ref145","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1016\/j.bmc.2019.07.029","article-title":"Rational modification of Mannich base-type derivatives as novel antichagasic compounds: synthesis, in vitro and in vivo evaluation","volume":"27","author":"Paucar R","year":"2019","journal-title":"Bioorg Med Chem"},{"key":"ref146","doi-asserted-by":"crossref","first-page":"113646","DOI":"10.1016\/j.ejmech.2021.113646","article-title":"Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas disease","volume":"223","author":"Beltran-Hortelano I","year":"2021","journal-title":"Eur J Med Chem"},{"issue":"21","key":"ref147","doi-asserted-by":"crossref","first-page":"13453","DOI":"10.1073\/pnas.202422899","article-title":"Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum","volume":"99","author":"Wilkinson SR","year":"2002","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"ref148","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1134\/S000629792301011X","article-title":"Allylpolyalkoxybenzene inhibitors of galactonolactone oxidase from Trypanosoma cruzi","volume":"88","author":"Chudin AA","year":"2023","journal-title":"Biochem Biokhimiia"},{"issue":"8","key":"ref149","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/acsinfecdis.2c00325","article-title":"Optimization of potent and specific trypanothione reductase inhibitors: a structure-based drug discovery approach","volume":"8","author":"Battista T","year":"2022","journal-title":"ACS Infect Dis"},{"issue":"20","key":"ref150","article-title":"Natural sesquiterpene lactones of the 4,15-iso-atriplicolide type are inhibitors of trypanothione reductase","volume":"24","author":"Lenz M","year":"2019","journal-title":"Mol Basel Switz"},{"issue":"10","key":"ref151","doi-asserted-by":"crossref","DOI":"10.1002\/minf.202300069","article-title":"Phenothiazine-based virtual screening, molecular docking, and molecular dynamics of new trypanothione reductase inhibitors of Trypanosoma cruzi","volume":"42","author":"Gonz\u00e1lez-Gonz\u00e1lez A","year":"2023","journal-title":"Mol Inform"},{"key":"ref152","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.freeradbiomed.2018.10.436","article-title":"Trypanothione synthetase confers growth, survival advantage and resistance to anti-protozoal drugs in Trypanosoma cruzi","volume":"130","author":"Mes\u00edas AC","year":"2019","journal-title":"Free Radic Biol Med"},{"issue":"16","key":"ref153","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1016\/j.bmc.2016.06.023","article-title":"5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms","volume":"24","author":"Orban OCF","year":"2016","journal-title":"Bioorg Med Chem"},{"issue":"4","key":"ref154","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004617","article-title":"Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids","volume":"10","author":"Ben\u00edtez D","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ref155","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-06411-9","article-title":"In silico, in vitro, X-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for Chagas disease","volume":"7","author":"Yoshino R","year":"2017","journal-title":"Sci Rep"},{"issue":"29","key":"ref156","doi-asserted-by":"crossref","first-page":"25850","DOI":"10.1021\/acsomega.3c01314","article-title":"Discovery of a hidden Trypanosoma cruzi spermidine synthase binding site and inhibitors through in silico, in vitro, and X-ray crystallography","volume":"8","author":"Yoshino R","year":"2023","journal-title":"ACS Omega"},{"issue":"1","key":"ref157","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.actatropica.2009.02.007","article-title":"Characterization of a gene encoding alcohol dehydrogenase in benznidazole-susceptible and -resistant populations of Trypanosoma cruzi","volume":"111","author":"Campos FMF","year":"2009","journal-title":"Acta Trop"},{"issue":"5","key":"ref158","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/mmi.13830","article-title":"Aldo-keto reductase and alcohol dehydrogenase contribute to benznidazole natural resistance in Trypanosoma cruzi","volume":"106","author":"Gonz\u00e1lez L","year":"2017","journal-title":"Mol Microbiol"},{"key":"ref159","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ceb.2021.12.007","article-title":"Plasticity in centromere organization and kinetochore composition: lessons from diversity","volume":"74","author":"Ishii M","year":"2022","journal-title":"Curr Opin Cell Biol"},{"issue":"5","key":"ref160","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0217828","article-title":"Identification of inhibitors of an unconventional Trypanosoma brucei kinetochore kinase","volume":"14","author":"Torrie LS","year":"2019","journal-title":"PLoS One"},{"key":"ref161","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116641","article-title":"DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents","volume":"276","author":"P\u00e9rez-Soto M","year":"2024","journal-title":"Eur J Med Chem"},{"key":"ref162","article-title":"4-Chlorophenylthioacetone-derived thiosemicarbazones as potent antitrypanosomal drug candidates: Investigations on the mode of action","volume":"113","author":"De Assis D","year":"2021","journal-title":"Bioorganic Chem"},{"issue":"12","key":"ref163","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010056","article-title":"\"Reading\" a new chapter in protozoan parasite transcriptional regulation","volume":"17","author":"Fleck K","year":"2021","journal-title":"PLoS Pathog"},{"key":"ref164","series-title":"Adv Exp Med Biol","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-0-387-77570-8_7","volume-title":"Histone deacetylases","volume":"625","author":"Horn D","year":"2008"},{"issue":"9","key":"ref165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004026","article-title":"Targeting lysine deacetylases (KDACs) in parasites","volume":"9","author":"Wang Q","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ref166","doi-asserted-by":"crossref","DOI":"10.1016\/j.micron.2024.103729","article-title":"Plant-derived compounds that target histone acetyltransferases inhibit Trypanosoma cruzi proliferation and viability and affect parasite ultrastructure","volume":"188","author":"Bortolami FP","year":"2025","journal-title":"Micron"},{"issue":"4","key":"ref167","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1017\/S0031182018001828","article-title":"Trichostatin A induces Trypanosoma cruzi histone and tubulin acetylation: effects on cell division and microtubule cytoskeleton remodelling","volume":"146","author":"De Oliveira Santos J","year":"2019","journal-title":"Parasitology"},{"issue":"36","key":"ref168","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.2174\/0929867325666181031132007","article-title":"Aim for the readers! Bromodomains as new targets against Chagas' disease","volume":"26","author":"Alonso VL","year":"2019","journal-title":"Curr Med Chem"},{"issue":"11","key":"ref169","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/acsinfecdis.3c00431","article-title":"Bromodomain factor 5 as a target for antileishmanial drug discovery","volume":"9","author":"Russell CN","year":"2023","journal-title":"ACS Infect Dis"},{"issue":"8","key":"ref170","doi-asserted-by":"crossref","DOI":"10.1128\/aac.00243-24","article-title":"Identification of novel bromodomain inhibitors of Trypanosoma cruzi bromodomain factor 2 (TcBDF2) using a fluorescence polarization-based high-throughput assay","volume":"68","author":"Tavernelli LE","year":"2024","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"ref171","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1101\/gad.1790409","article-title":"Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei","volume":"23","author":"Siegel TN","year":"2009","journal-title":"Genes Dev"},{"issue":"2","key":"ref172","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.molbiopara.2013.09.005","article-title":"Kinetoplastid-specific histone variant functions are conserved in Leishmania major","volume":"191","author":"Anderson BA","year":"2013","journal-title":"Mol Biochem Parasitol"},{"issue":"10","key":"ref173","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0078886","article-title":"DNA aptamers selectively target Leishmania infantum H2A protein","volume":"8","author":"Mart\u00edn ME","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"ref174","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1590\/S0074-02762011000300002","article-title":"Regulatory elements involved in the post-transcriptional control of stage-specific gene expression in Trypanosoma cruzi: A Review","volume":"106","author":"Ara\u00fajo PR","year":"2011","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"3","key":"ref175","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.resmic.2014.01.006","article-title":"Dealing with environmental challenges: mechanisms of adaptation in Trypanosoma cruzi","volume":"165","author":"Jimenez V","year":"2014","journal-title":"Res Microbiol"},{"issue":"2","key":"ref176","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000067741","article-title":"Trypanosoma cruzi: in vitro morphological alterations induced by actinomycin D","volume":"67","author":"Do Valle TZ","year":"2003","journal-title":"Pharmacology"},{"key":"ref177","first-page":"5941","article-title":"Functionalization of immunostimulating complexes (ISCOMs) with lipid vinyl sulfones and their application in immunological techniques and therapy","volume":"7","author":"Cruz-Bustos T","year":"2012","journal-title":"Int J Nanomedicine"},{"issue":"6","key":"ref178","doi-asserted-by":"crossref","DOI":"10.3390\/ph18060845","article-title":"In silico investigation of TATA-binding protein as a therapeutic target for Chagas disease: insights into FDA drug repositioning","volume":"18","author":"Gaona-L\u00f3pez C","year":"2025","journal-title":"Pharmaceuticals"},{"issue":"9","key":"ref179","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007315","article-title":"The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing","volume":"14","author":"Begolo D","year":"2018","journal-title":"PLoS Pathog"},{"issue":"38","key":"ref180","doi-asserted-by":"crossref","first-page":"9616","DOI":"10.1073\/pnas.1807915115","article-title":"Clinical and veterinary trypanocidal benzoxaboroles target CPSF3","volume":"115","author":"Wall RJ","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"ref181","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1038\/s41564-022-01211-y","article-title":"Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates","volume":"7","author":"Padilla AM","year":"2022","journal-title":"Nat Microbiol"},{"key":"ref182","article-title":"RNA binding proteins and gene expression regulation in Trypanosoma cruzi","volume":"10","author":"Romagnoli BAA","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"3","key":"ref183","article-title":"TcZC3HTTP, a regulatory element that contributes to Trypanosoma cruzi cell proliferation","volume":"12","author":"Romagnoli BAA","year":"2024","journal-title":"Microbiol Spectr"},{"issue":"3","key":"ref184","first-page":"278","article-title":"PUF proteins as critical RNA-binding proteins in TriTryp parasites: a review article","volume":"19","author":"Taheri T","year":"2024","journal-title":"Iran J Parasitol"},{"issue":"14","key":"ref185","doi-asserted-by":"crossref","first-page":"7520","DOI":"10.1093\/nar\/gkad497","article-title":"A unique mRNA decapping complex in trypanosomes","volume":"51","author":"Kramer S","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"ref186","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae1181","article-title":"Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress","volume":"53","author":"Gabiatti BP","year":"2025","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"ref187","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens6040055","article-title":"The role of cytoplasmic mRNA cap-binding protein complexes in Trypanosoma brucei and other trypanosomatids","volume":"6","author":"Freire E","year":"2017","journal-title":"Pathogens"},{"issue":"5","key":"ref188","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1039\/C9NP00052F","article-title":"Selective targeting of the DEAD-box RNA helicase eukaryotic initiation factor (eIF) 4A by natural products","volume":"37","author":"Shen L","year":"2020","journal-title":"Nat Prod Rep"},{"issue":"9","key":"ref189","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760180162","article-title":"Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations","volume":"113","author":"Moreira DS","year":"2018","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref190","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2091-12-46","article-title":"The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles into a homohexamer and belongs to the M17 family of metallopeptidases","volume":"12","author":"Cadavid-Restrepo G","year":"2011","journal-title":"BMC Biochem"},{"issue":"2","key":"ref191","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011956","article-title":"Identification of a potent and selective LAPTc inhibitor by RapidFire-Mass Spectrometry, with antichagasic activity","volume":"18","author":"Izquierdo M","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"ref192","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.108080","article-title":"Inhibition of L-threonine dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability","volume":"301","author":"Faria JN","year":"2025","journal-title":"J Biol Chem"},{"issue":"806","key":"ref193","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adu4564","article-title":"Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease","volume":"17","author":"Tulloch LB","year":"2025","journal-title":"Sci Transl Med"},{"issue":"6","key":"ref194","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1128\/EC.1.6.936-943.2002","article-title":"Inhibition of HSP90 in Trypanosoma cruzi induces a stress response but no stage differentiation","volume":"1","author":"Graefe SEB","year":"2002","journal-title":"Eukaryot Cell"},{"issue":"2","key":"ref195","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22020688","article-title":"Anti-Trypanosoma cruzi activity of metabolism modifier compounds","volume":"22","author":"Martinez-Peinado N","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"4","key":"ref196","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003725","article-title":"Overexpression of cytoplasmic TcSIR2RP1 and mitochondrial TcSIR2RP3 impacts on Trypanosoma cruzi growth and cell invasion","volume":"9","author":"Ritagliati C","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ref197","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006180","article-title":"Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease","volume":"12","author":"Gaspar L","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"ref198","article-title":"Ubiquitination and the proteasome as drug targets in trypanosomatid diseases","volume":"8","author":"Bijlmakers MJ","year":"2020","journal-title":"Front Chem"},{"issue":"19","key":"ref199","doi-asserted-by":"crossref","first-page":"9318","DOI":"10.1073\/pnas.1820175116","article-title":"Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition","volume":"116","author":"Wyllie S","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"issue":"9","key":"ref200","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00309-19","article-title":"Identification of novel Trypanosoma cruzi proteasome inhibitors using a luminescence-based high-throughput screening assay","volume":"63","author":"Zmuda F","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"ref201","doi-asserted-by":"crossref","DOI":"10.1038\/srep08771","article-title":"New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource","volume":"5","author":"Pe\u00f1a I","year":"2015","journal-title":"Sci Rep"},{"issue":"Pt 3","key":"ref202","article-title":"Structural analysis and shape-based identification of novel inhibitors targeting the Trypanosoma cruzi proteasome","volume":"277","author":"Silva GM","year":"2024","journal-title":"Int J Biol Macromol"},{"issue":"7","key":"ref203","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25073747","article-title":"Integrated computational approaches for drug design targeting cruzipain","volume":"25","author":"Parvez A","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"ref204","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1021\/acsmedchemlett.4c00460","article-title":"Discovery of a potent triazole-based reversible targeted covalent inhibitor of cruzipain","volume":"16","author":"Cerutti JP","year":"2025","journal-title":"ACS Med Chem Lett"},{"issue":"3","key":"ref205","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1021\/acsmedchemlett.4c00631","article-title":"Thiosulfonate-based targeted covalent cruzipain inhibitors with enhanced bioactivity translation for antichagasic therapy","volume":"16","author":"Cerutti JP","year":"2025","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"ref206","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11030-020-10156-5","article-title":"Synthesis and biological evaluation in vitro and in silico of N-propionyl-N'-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi","volume":"26","author":"Delgado-Maldonado T","year":"2022","journal-title":"Mol Divers"},{"issue":"23","key":"ref207","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202400241","article-title":"Design, synthesis, and in vitro and in silico evaluation of 1,3,4-oxadiazoles as anti-Trypanosoma cruzi and anti-Leishmania mexicana agents","volume":"19","author":"Delgado-Maldonado T","year":"2024","journal-title":"ChemMedChem"},{"issue":"12","key":"ref208","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.2174\/1381612013397528","article-title":"The major cysteine proteinase of Trypanosoma cruzi: a valid target for chemotherapy of Chagas disease","volume":"7","author":"Cazzulo JJ","year":"2001","journal-title":"Curr Pharm Des"},{"key":"ref209","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev.mi.48.100194.002435","article-title":"Structural and functional properties of Trypanosoma trans-sialidase","volume":"48","author":"Schenkman S","year":"1994","journal-title":"Annu Rev Microbiol"},{"issue":"10","key":"ref210","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1111\/j.1462-5822.2012.01831.x","article-title":"Trypanosoma cruzi trans-sialidase as a multifunctional enzyme in Chagas' disease: Trypanosoma cruzi trans-sialidase as a multifunctional enzyme","volume":"14","author":"dC-Rubin SSC","year":"2012","journal-title":"Cell Microbiol"},{"issue":"10","key":"ref211","doi-asserted-by":"crossref","DOI":"10.3390\/genes11101196","article-title":"Trypanosoma cruzi genome: organization, multi-gene families, transcription, and biological implications","volume":"11","author":"Herreros-Cabello A","year":"2020","journal-title":"Genes"},{"issue":"5","key":"ref212","article-title":"Parasite-host glycan interactions during Trypanosoma cruzi infection: trans-sialidase rides the show","volume":"1866","author":"Campetella O","year":"2020","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"ref213","article-title":"Disruption of active trans-sialidase genes impairs egress from mammalian host cells and generates highly attenuated Trypanosoma cruzi parasites","volume":"13","author":"Burle-Caldas GA","year":"2022","journal-title":"mBio"},{"issue":"15","key":"ref214","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1021\/bi802230y","article-title":"Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase","volume":"48","author":"Demir \u00d6","year":"2009","journal-title":"Biochemistry"},{"issue":"12","key":"ref215","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.carres.2011.04.006","article-title":"Trans-sialidase and mucins of Trypanosoma cruzi: an important interplay for the parasite","volume":"346","author":"Giorgi E","year":"2011","journal-title":"Carbohydr Res"},{"key":"ref216","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejmech.2018.08.089","article-title":"The synthesis and kinetic evaluation of aryl \u03b1-aminophosphonates as novel inhibitors of T. cruzi trans-sialidase","volume":"158","author":"Chen Z","year":"2018","journal-title":"Eur J Med Chem"},{"issue":"1","key":"ref217","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bmc.2011.11.022","article-title":"Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase","volume":"20","author":"Campo VL","year":"2012","journal-title":"Bioorg Med Chem"},{"key":"ref218","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.3762\/bjoc.10.324","article-title":"Synthesis of divalent ligands of \u03b2-thio- and \u03b2-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase","volume":"10","author":"Cano ME","year":"2014","journal-title":"Beilstein J Org Chem"},{"issue":"18","key":"ref219","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.1016\/j.bmcl.2014.07.088","article-title":"Design, synthesis and enzymatic evaluation of 3-O-substituted aryl \u03b2-d-galactopyranosides as inhibitors of Trypanosoma cruzi trans-sialidase","volume":"24","author":"Silva BL","year":"2014","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"ref220","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.bmcl.2008.12.065","article-title":"Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening","volume":"19","author":"Neres J","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"issue":"7","key":"ref221","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2174\/1573406416666200506084611","article-title":"Structure-based virtual screening of new benzoic acid derivatives as Trypanosoma cruzi trans-sialidase inhibitors","volume":"17","author":"V\u00e1zquez-Jim\u00e9nez LK","year":"2021","journal-title":"Med Chem"},{"key":"ref222","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ejmech.2018.07.005","article-title":"Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase","volume":"156","author":"Kashif M","year":"2018","journal-title":"Eur J Med Chem"},{"key":"ref223","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2021.725892","article-title":"Benzopyrazine-based small molecule inhibitors as trypanocidal and leishmanicidal agents: green synthesis, in vitro, and in silico evaluations","volume":"9","author":"Rock J","year":"2021","journal-title":"Front Chem"},{"key":"ref224","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jmgm.2013.08.009","article-title":"Design of e-pharmacophore models using compound fragments for the trans-sialidase of Trypanosoma cruzi: screening for novel inhibitor scaffolds","volume":"45","author":"Miller BR","year":"2013","journal-title":"J Mol Graph Model"},{"key":"ref225","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ejmech.2017.03.063","article-title":"An in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of Trypanosoma cruzi predicted by a computational drug repositioning method","volume":"132","author":"Lara-Ramirez EE","year":"2017","journal-title":"Eur J Med Chem"},{"issue":"3","key":"ref226","article-title":"Identification of potential Trypanosoma cruzi trans-sialidase inhibitors by computational drug repositioning approaches","volume":"92","author":"Uc-Chuc MA","year":"2024","journal-title":"Sci Pharm"},{"key":"ref227","series-title":"Subcell Biochem","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/978-94-007-7305-9_11","volume-title":"GP63 function in the interaction of trypanosomatids with the invertebrate host: facts and prospects","volume":"74","author":"d'Avila-Levy CM","year":"2014"},{"issue":"1","key":"ref228","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-90088-y","article-title":"In silico evaluation of N-aryl-1,10-phenanthroline-2-amines as potential inhibitors of T. cruzi GP63 zinc-metalloprotease by docking and molecular dynamics simulations","volume":"15","author":"Camargo PG","year":"2025","journal-title":"Sci Rep"},{"issue":"3","key":"ref229","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0012950","article-title":"Exploring the genomic landscape of the GP63 family in Trypanosoma cruzi: evolutionary dynamics and functional peculiarities","volume":"19","author":"Bern\u00e1 L","year":"2025","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"ref230","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1021\/acs.jcim.4c02152","article-title":"Structure-based identification of non-covalent prolyl oligopeptidase 80 inhibitors targeting Trypanosoma cruzi cell entry","volume":"65","author":"Costa VAF","year":"2025","journal-title":"J Chem Inf Model"},{"issue":"13","key":"ref231","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1073\/pnas.0711014105","article-title":"A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes","volume":"105","author":"Wilkinson SR","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"ref232","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.molbiopara.2014.01.002","article-title":"Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert","volume":"193","author":"Campos MCO","year":"2014","journal-title":"Mol Biochem Parasitol"},{"issue":"5","key":"ref233","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s12192-019-01018-7","article-title":"Quantitative phosphoproteome and proteome analyses emphasize the influence of phosphorylation events during the nutritional stress of Trypanosoma cruzi: the initial moments of in vitro metacyclogenesis","volume":"24","author":"Lucena ACR","year":"2019","journal-title":"Cell Stress Chaperones"},{"issue":"2","key":"ref234","article-title":"GSK-3 kinase a putative therapeutic target in trypanosomatid parasites","volume":"28","author":"Diaz AP","year":"2024","journal-title":"Braz J Infect Dis"},{"issue":"2","key":"ref235","article-title":"A membrane-bound eIF2 alpha kinase located in endosomes is regulated by heme and controls differentiation and ROS levels in Trypanosoma cruzi","volume":"11","author":"Augusto LS","year":"2015","journal-title":"PLoS Pathog"},{"issue":"7","key":"ref236","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.104857","article-title":"Identification of inhibitors for the transmembrane Trypanosoma cruzi eIF2\u03b1 kinase relevant for parasite proliferation","volume":"299","author":"Marcelino TP","year":"2023","journal-title":"J Biol Chem"},{"issue":"16","key":"ref237","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.4155\/fmc-2023-0090","article-title":"Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations","volume":"15","author":"Torchelsen FKVS","year":"2023","journal-title":"Future Med Chem"},{"key":"ref238","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.00149","article-title":"GCN2-like kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi","volume":"10","author":"Malvezzi AM","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"4","key":"ref239","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001017","article-title":"Trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: a public-private partnership to identify novel leads","volume":"5","author":"Oduor RO","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ref240","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-59654-8","article-title":"Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease","volume":"14","author":"Stadler KA","year":"2024","journal-title":"Sci Rep"},{"issue":"6","key":"ref241","doi-asserted-by":"crossref","DOI":"10.1111\/jeu.12999","article-title":"Gene editing of putative cAMP and Ca2+-regulated proteins using an efficient cloning-free CRISPR\/Cas9 system in Trypanosoma cruzi","volume":"70","author":"Chiurillo MA","year":"2023","journal-title":"J Eukaryot Microbiol"},{"issue":"1","key":"ref242","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.202400626","article-title":"The carbonic anhydrase enzymes as new targets for the management of neglected tropical diseases","volume":"358","author":"Renzi G","year":"2025","journal-title":"Arch Pharm (Weinheim)"},{"issue":"1","key":"ref243","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/14756366.2019.1677638","article-title":"A structure-based approach towards the identification of novel antichagasic compounds: Trypanosoma cruzi carbonic anhydrase inhibitors","volume":"35","author":"Llanos MA","year":"2020","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"10","key":"ref244","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1021\/acs.jcim.5c00279","article-title":"Discovery of Trypanosoma cruzi carbonic anhydrase inhibitors by a combination of ligand- and structure-based virtual screening","volume":"65","author":"Prada Gori DN","year":"2025","journal-title":"J Chem Inf Model"},{"issue":"4","key":"ref245","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.exppara.2012.12.005","article-title":"Evaluation of the in vivo therapeutic properties of (\u2212)-cubebin and (\u2212)-hinokinin against Trypanosoma cruzi","volume":"133","author":"Esperandim VR","year":"2013","journal-title":"Exp Parasitol"},{"key":"ref246","series-title":"[Portfolio]"},{"issue":"4","key":"ref247","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1473-3099(23)00651-5","article-title":"Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial","volume":"24","author":"Pinazo MJ","year":"2024","journal-title":"Lancet Infect Dis"},{"issue":"14","key":"ref248","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1056\/NEJMoa1507574","article-title":"Randomized trial of benznidazole for chronic Chagas' cardiomyopathy","volume":"373","author":"Morillo CA","year":"2015","journal-title":"N Engl J Med"},{"issue":"4","key":"ref249","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S1473-3099(23)00629-1","article-title":"Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial","volume":"24","author":"Bosch-Nicolau P","year":"2024","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"ref250","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S1473-3099(20)30844-6","article-title":"New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial","volume":"21","author":"Torrico F","year":"2021","journal-title":"Lancet Infect Dis"},{"issue":"9","key":"ref251","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-098079","article-title":"New regimens of benznidazole for the treatment of chronic Chagas disease in adult participants in indeterminate form or with mild cardiac progression (NuestroBen study): protocol for a phase III randomised, multicentre non-inferiority clinical trial","volume":"15","author":"Marques T","year":"2025","journal-title":"BMJ Open"},{"key":"ref252"},{"key":"ref253","author":"Veras N","year":"2025"},{"key":"ref254","doi-asserted-by":"crossref","DOI":"10.1016\/j.actatropica.2019.105107","article-title":"Drug discovery for chagas disease: a viewpoint","volume":"198","author":"Kratz JM","year":"2019","journal-title":"Acta Trop"},{"issue":"2","key":"ref255","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.meegid.2011.12.009","article-title":"The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications","volume":"12","author":"Zingales B","year":"2012","journal-title":"Infect Genet Evol"},{"issue":"1","key":"ref256","doi-asserted-by":"crossref","DOI":"10.1186\/1756-3305-4-169","article-title":"Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benznidazole in Trypanosoma cruzi","volume":"4","author":"Mej\u00eda-Jaramillo AM","year":"2011","journal-title":"Parasit Vectors"},{"issue":"2","key":"ref257","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.molbiopara.2005.12.001","article-title":"Deletion of copies of the gene encoding old yellow enzyme (TcOYE), a NAD(P)H flavin oxidoreductase, associates with in vitro-induced benznidazole resistance in Trypanosoma cruzi","volume":"146","author":"Murta SMF","year":"2006","journal-title":"Mol Biochem Parasitol"},{"issue":"1-2","key":"ref258","doi-asserted-by":"crossref","DOI":"10.1016\/j.micinf.2023.105240","article-title":"Trypanosoma cruzi amastigote transcriptome analysis reveals heterogenous populations with replicating and dormant parasites","volume":"26","author":"Desale H","year":"2024","journal-title":"Microbes Infect"},{"issue":"11","key":"ref259","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011627","article-title":"Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice","volume":"19","author":"Jayawardhana S","year":"2023","journal-title":"PLOS Pathog"},{"key":"ref260","article-title":"Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure","volume":"7","author":"S\u00e1nchez-Vald\u00e9z FJ","year":"2018","journal-title":"eLife"},{"issue":"Suppl. 1","key":"ref261","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1590\/S0074-02762009000900041","article-title":"Ergosterol biosynthesis and drug development for Chagas disease","volume":"104","author":"Urbina JA","year":"2009","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"3","key":"ref262","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0035-9203(82)90184-5","article-title":"Effect of specific chemotherapy on the levels of lytic antibodies in Chagas's disease","volume":"76","author":"Krettli AU","year":"1982","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"1","key":"ref263","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1128\/CDLI.8.1.112-118.2001","article-title":"Anti-Trypanosoma cruzi immunoglobulin G1 can be a useful tool for diagnosis and prognosis of human Chagas' disease","volume":"8","author":"Cordeiro FD","year":"2001","journal-title":"Clin Diagn Lab Immunol"},{"issue":"6","key":"ref264","doi-asserted-by":"crossref","DOI":"10.3390\/life13061236","article-title":"Validation of the NAT Chagas IVD Kit for the detection and quantification of Trypanosoma cruzi in blood samples of patients with Chagas disease","volume":"13","author":"Moreira OC","year":"2023","journal-title":"Life"},{"issue":"3","key":"ref265","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00520-21","article-title":"mSphere of influence: forgotten questions","volume":"6","author":"McCall LI","year":"2021","journal-title":"mSphere"},{"issue":"3","key":"ref266","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1590\/0037-8682-0433-2016","article-title":"Chagas disease: review of needs, neglect, and obstacles to treatment access in Latin America","volume":"50","author":"Pinheiro E","year":"2017","journal-title":"Rev Soc Bras Med Trop"},{"key":"ref267","doi-asserted-by":"crossref","DOI":"10.1016\/j.actatropica.2019.105062","article-title":"Genomic medicine in Chagas disease","volume":"197","author":"Acosta-Herrera M","year":"2019","journal-title":"Acta Trop"},{"key":"ref268","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.00210","article-title":"Precision health for Chagas disease: integrating parasite and host factors to predict outcome of infection and response to therapy","volume":"10","author":"Martinez SJ","year":"2020","journal-title":"Front Cell Infect Microbiol"}],"container-title":["Mem\u00f3rias do Instituto Oswaldo Cruz"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0074-02762026001201001&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T10:44:29Z","timestamp":1783680269000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0074-02762026001201001&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":268,"journal-issue":{"issue":"suppl 2","published-online":{"date-parts":[[2026]]}},"alternative-id":["S0074-02762026001201001"],"URL":"https:\/\/doi.org\/10.1590\/0074-02760250299","relation":{},"ISSN":["1678-8060","0074-0276"],"issn-type":[{"value":"1678-8060","type":"electronic"},{"value":"0074-0276","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"e250299"}}