{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:26:23Z","timestamp":1774506383548,"version":"3.50.1"},"reference-count":123,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.ejmech.2024.117203","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T07:15:33Z","timestamp":1735370133000},"page":"117203","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Synthesis strategies and anti-parasitic evaluation of novel compounds for chagas disease: Advancing drug discovery through structure-activity relationships"],"prefix":"10.1016","volume":"284","author":[{"given":"Jitendra","family":"Chaudhary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurdeep","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2838-1741","authenticated-orcid":false,"given":"Iqubal","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2024.117203_bib1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12916-023-02885-9","article-title":"Putting Chagas disease on the global health agenda","volume":"21","author":"com","year":"2023","journal-title":"BMC Med."},{"key":"10.1016\/j.ejmech.2024.117203_bib2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3390\/parasitologia3020013","article-title":"Analysis of the perception of Brazilian medical students about chagas disease","volume":"3","author":"Clovis","year":"2023","journal-title":"Parasitologia"},{"key":"10.1016\/j.ejmech.2024.117203_bib3","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760220066","article-title":"How people affected by Chagas disease have struggled with their negligence: history, associative movement and World Chagas Disease Day","volume":"117","author":"de Oliveira Junior","year":"2022","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"10.1016\/j.ejmech.2024.117203_bib4","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1021\/acsinfecdis.2c00123","article-title":"An updated view of the trypanosoma cruzi life cycle: intervention points for an effective treatment","volume":"8","author":"Mart\u00edn-Escolano","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib5","doi-asserted-by":"crossref","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","year":"2022","journal-title":"Biorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s40475-022-00261-w","article-title":"Our current understanding of chagas disease and trypanosoma cruzi infection in the state of Florida\u2014an update on research in this region of the USA, curr","volume":"9","author":"Beatty","year":"2022","journal-title":"Trop. Med. Rep"},{"key":"10.1016\/j.ejmech.2024.117203_bib7","doi-asserted-by":"crossref","first-page":"736","DOI":"10.2174\/1568026623666230201103843","article-title":"Structural insight into privileged heterocycles as anti-trypanosoma cruzi and brucei agents","volume":"23","author":"Abbasi Shiran","year":"2023","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib8","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.3390\/microorganisms10051003","article-title":"The parasite load of Trypanosoma cruzi modulates feeding and defecation patterns of the Chagas disease vector Triatoma infestans","volume":"10","author":"Chac\u00f3n","year":"2022","journal-title":"Microorganisms"},{"key":"10.1016\/j.ejmech.2024.117203_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.actatropica.2023.107039","article-title":"Diet of the sylvatic triatomine Mepraia spinolai: association with Trypanosoma cruzi infection near human settlements","author":"Sierra-Rosales","year":"2023","journal-title":"Acta Trop."},{"key":"10.1016\/j.ejmech.2024.117203_bib10","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1021\/acsinfecdis.0c00353","article-title":"Chagas disease: current view of an ancient and global chemotherapy challenge","volume":"6","author":"Mart\u00edn-Escolano","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib11","article-title":"Alternative approaches for the treatment of chagas disease","volume":"9","author":"Chaudhary","year":"2024","journal-title":"Chem. Select."},{"key":"10.1016\/j.ejmech.2024.117203_bib13","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/9781118777329.ch72","article-title":"Trypanosomiasis","author":"Carod\u2010Artal","year":"2016","journal-title":"Int. Neurol."},{"key":"10.1016\/j.ejmech.2024.117203_bib14","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2019.00166","article-title":"Chagas disease: from discovery to a worldwide health problem","volume":"7","author":"Lidani","year":"2019","journal-title":"Front. Public Health"},{"key":"10.1016\/j.ejmech.2024.117203_bib16","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.3390\/ijms25073840","article-title":"Chagas disease: a silent threat for dogs and humans","volume":"25","author":"Dur\u00e3es-Oliveira","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2024.117203_bib17","doi-asserted-by":"crossref","DOI":"10.1590\/0074-02760210034","article-title":"Critical analysis of Chagas disease treatment in different countries","volume":"117","author":"Mendes","year":"2022","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"10.1016\/j.ejmech.2024.117203_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114576","article-title":"Seeking heterocyclic scaffolds as antivirals against dengue virus","volume":"240","author":"De","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116896","article-title":"An insight into recent developments in imidazole based heterocyclic compounds as anticancer agents: synthesis, SARs, and mechanism of actions","author":"Kumar","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejmech.2016.09.023","article-title":"Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities","volume":"125","author":"Akhtar","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib21","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3390\/pharmaceutics15030754","article-title":"Exploring synthetic dihydrobenzofuran and benzofuran neolignans as antiprotozoal agents against trypanosoma cruzi","volume":"15","author":"Pagotti","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.ejmech.2024.117203_bib22","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.3390\/molecules27072163","article-title":"Synthesis and anti-trypanosoma cruzi biological evaluation of novel 2-nitropyrrole derivatives","volume":"27","author":"Mathias","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2024.117203_bib23","first-page":"238","article-title":"Tandem synthesis of furanaphthoquinones via enamines and evaluation of their antiparasitic effects against trypanosoma cruzi","volume":"33","author":"Cardoso","year":"2022","journal-title":"J. Braz. Chem. Soc."},{"key":"10.1016\/j.ejmech.2024.117203_bib24","article-title":"Trypanosoma evansi and surra: a review and perspectives on origin, history, distribution, taxonomy, morphology, hosts, and pathogenic effects","volume":"2013","author":"Desquesnes","year":"2013","journal-title":"BioMedi Res. Int."},{"key":"10.1016\/j.ejmech.2024.117203_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003975","article-title":"Global gene expression profiling through the complete life cycle of Trypanosoma vivax","volume":"9","author":"Jackson","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib26","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1128\/9781555817381.ch137","article-title":"Leishmania and trypanosoma","author":"Bruckner","year":"2015","journal-title":"Manual of clinical microbiology"},{"key":"10.1016\/j.ejmech.2024.117203_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007059","article-title":"Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi","volume":"14","author":"Romaniuk","year":"2018","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ejmech.2024.117203_bib28","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1038\/s41467-022-33108-z","article-title":"A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission","volume":"13","author":"Bachmaier","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2024.117203_bib29","series-title":"W.H. Organization, the Triatomine Bugs: Biology and Control","author":"Schofield","year":"1987"},{"key":"10.1016\/j.ejmech.2024.117203_bib30","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/507874","article-title":"The immune response to Trypanosoma cruzi: role of toll\u2010like receptors and perspectives for vaccine development","volume":"2012","author":"Rodrigues","year":"2012","journal-title":"J. Parasit. Res."},{"key":"10.1016\/j.ejmech.2024.117203_bib31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1582-4934.2008.00388.x","article-title":"Acute heart inflammation: ultrastructural and functional aspects of macrophages elicited by Trypanosoma cruzi infection","volume":"13","author":"Melo","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.ejmech.2024.117203_bib32","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1600-065X.2010.00990.x","article-title":"Invasion and intracellular survival by protozoan parasites","volume":"240","author":"David Sibley","year":"2011","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.ejmech.2024.117203_bib33","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/1356540","article-title":"Intracellular pathogens: host immunity and microbial persistence strategies","volume":"2019","author":"Thakur","year":"2019","journal-title":"J. Immunol. Res."},{"key":"10.1016\/j.ejmech.2024.117203_bib34","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1590\/S0074-02762006000500001","article-title":"Evolution and pathology in Chagas disease: a review","volume":"101","author":"Teixeira","year":"2006","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"10.1016\/j.ejmech.2024.117203_bib35","doi-asserted-by":"crossref","first-page":"e618","DOI":"10.1371\/journal.pntd.0000618","article-title":"Complete in vitro life cycle of Trypanosoma congolense: development of genetic tools","volume":"4","author":"Coustou","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib36","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1126\/science.1198077","article-title":"Controlling and coordinating development in vector-transmitted parasites","volume":"331","author":"Matthews","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2024.117203_bib37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2015.07.018","article-title":"The multiple and complex and changeable scenarios of the Trypanosoma cruzi transmission cycle in the sylvatic environment","volume":"151","author":"Jansen","year":"2015","journal-title":"Acta Trop."},{"key":"10.1016\/j.ejmech.2024.117203_bib38","series-title":"Research Priorities for Chagas Disease, Human African Trypanosomiasis and Leishmaniasis","author":"Organization","year":"2012"},{"key":"10.1016\/j.ejmech.2024.117203_bib39","series-title":"Control and Surveillance of Human African Trypanosomiasis: Report of a WHO Expert Committee","year":"2013"},{"key":"10.1016\/j.ejmech.2024.117203_bib40","series-title":"Forging the Chain: Scenes from the Battle against Neglected Tropical Diseases, with the Support of Innovative Partners","author":"Organization","year":"2016"},{"key":"10.1016\/j.ejmech.2024.117203_bib41","series-title":"Kucers' the Use of Antibiotics","first-page":"3271","article-title":"Pentamidine","author":"Woods","year":"2017"},{"key":"10.1016\/j.ejmech.2024.117203_bib42","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","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001204","article-title":"A molecular mechanism for eflornithine resistance in African trypanosomes","volume":"6","author":"Vincent","year":"2010","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ejmech.2024.117203_bib44","series-title":"Chagas' Disease and Trypanosomiasis, Harrison's Principles of Internal Medicine","first-page":"1716","author":"Kirchhoff","year":"2012"},{"key":"10.1016\/j.ejmech.2024.117203_bib45","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.202100338","article-title":"Antiprotozoal agents: how have they changed over a decade?","volume":"355","author":"Fernandes","year":"2022","journal-title":"Arch. Pharm."},{"key":"10.1016\/j.ejmech.2024.117203_bib46","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/europace\/eut422","article-title":"Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with Chagas' heart disease: comparison with a control group treated with amiodarone alone","volume":"16","author":"Gali","year":"2014","journal-title":"Europace"},{"key":"10.1016\/j.ejmech.2024.117203_bib47","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1017\/S0031182022001081","article-title":"Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials","volume":"149","author":"Nogueira","year":"2022","journal-title":"Parasitology"},{"key":"10.1016\/j.ejmech.2024.117203_bib48","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2023.1295017","article-title":"Clinical trials for Chagas disease: etiological and pathophysiological treatment","volume":"14","author":"Gonzaga","year":"2023","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.ejmech.2024.117203_bib49","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1517\/17460441.2013.845554","article-title":"Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?","volume":"8","author":"Lepesheva","year":"2013","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2024.117203_bib50","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.2174\/1568026621666210920155939","article-title":"Recent studies on neglected drug design","volume":"21","author":"de Sousa","year":"2021","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib51","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1093\/jac\/dkp357","article-title":"Use of benznidazole to treat chronic Chagas' disease: a systematic review with a meta-analysis","volume":"64","author":"P\u00e9rez-Molina","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.ejmech.2024.117203_bib52","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/bcp.14700","article-title":"Review of pharmacological options for the treatment of Chagas disease","volume":"88","author":"Lascano","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejmech.2024.117203_bib53","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/978-3-030-00054-7_14","article-title":"Clinical pharmacology of drugs for the treatment of chagas disease","author":"Garcia-Bournissen","year":"2019","journal-title":"Chagas Disease: A Clinical Approach"},{"key":"10.1016\/j.ejmech.2024.117203_bib54","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002907","article-title":"Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults","volume":"8","author":"Altcheh","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib56","series-title":"WHO Model List of Essential Medicines for Children: 4th List, April 2013","year":"2013"},{"key":"10.1016\/j.ejmech.2024.117203_bib57","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008912","article-title":"Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)","volume":"15","author":"Altcheh","year":"2021","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib58","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1080\/15384047.2015.1070987","article-title":"Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma","volume":"16","author":"Cabanillas Stanchi","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.ejmech.2024.117203_bib59","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1128\/AAC.01129-10","article-title":"Amiodarone inhibits Trypanosoma cruzi infection and promotes cardiac cell recovery with gap junction and cytoskeleton reassembly in vitro","volume":"55","author":"Adesse","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2024.117203_bib60","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1179\/000349803125002751","article-title":"Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis: the regression and prevention of electrocardiographic abnormalities during 9 years of follow-up","volume":"97","author":"Apt","year":"2003","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"10.1016\/j.ejmech.2024.117203_bib61","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","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2024.117203_bib62","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","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib63","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001870","article-title":"Fexinidazole: a potential new drug candidate for Chagas disease","volume":"6","author":"Bahia","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2024.117203_bib64","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrmicro.2016.193","article-title":"Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need","volume":"15","author":"Field","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2024.117203_bib65","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/292138","article-title":"Therapy of Chagas disease: implications for levels of prevention","volume":"2012","author":"Sosa-Estani","year":"2012","journal-title":"J. Trop. Med."},{"key":"10.1016\/j.ejmech.2024.117203_bib66","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3389\/fphar.2016.00351","article-title":"New approaches to overcome transport related drug resistance in trypanosomatid parasites","volume":"7","author":"Garcia-Salcedo","year":"2016","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2024.117203_bib67","series-title":"Annu. Rep. Med. Chem.","first-page":"97","article-title":"Drugs and drug resistance in African and American trypanosomiasis","author":"Franco","year":"2018"},{"key":"10.1016\/j.ejmech.2024.117203_bib68","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.drudis.2016.06.021","article-title":"Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective","volume":"21","author":"Ferreira","year":"2016","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2024.117203_bib69","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1039\/D0MD00122H","article-title":"Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases","volume":"11","author":"Parthasarathy","year":"2020","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib70","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1007\/s12011-023-03797-8","article-title":"Serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis: a systematic review and meta-analysis","volume":"202","author":"Pal","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"10.1016\/j.ejmech.2024.117203_bib71","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-14986-6","article-title":"Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole","volume":"7","author":"Campos","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2024.117203_bib72","series-title":"Advances in Antiparasitic Therapies and Drug Delivery","first-page":"289","article-title":"Antimicrobial resistance and recent advancement to combat parasitic infections; development of resistance to antihelminthic\/antiprotozoal and antimalarial drugs","author":"Singh","year":"2024"},{"key":"10.1016\/j.ejmech.2024.117203_bib73","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.ijpara.2007.05.007","article-title":"Melarsoprol-and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance","volume":"37","author":"Bernhard","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"10.1016\/j.ejmech.2024.117203_bib74","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.pt.2018.04.002","article-title":"Melarsoprol resistance in African trypanosomiasis","volume":"34","author":"Fairlamb","year":"2018","journal-title":"Trends Parasitol."},{"key":"10.1016\/j.ejmech.2024.117203_bib75","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ijpddr.2018.08.002","article-title":"Resistance of Leishmania infantum to allopurinol is associated with chromosome and gene copy number variations including decrease in the S-adenosylmethionine synthetase (METK) gene copy number","volume":"8","author":"Yasur-Landau","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"10.1016\/j.ejmech.2024.117203_bib76","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ijpddr.2020.06.001","article-title":"Novel structural CYP51 mutation in Trypanosoma cruzi associated with multidrug resistance to CYP51 inhibitors and reduced infectivity","volume":"13","author":"Franco","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"10.1016\/j.ejmech.2024.117203_bib77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00044-012-0010-5","article-title":"Molecular drug design, synthesis and pharmacophore site identification of spiroheterocyclic compounds: trypanosoma crusi inhibiting studies","volume":"22","author":"Ben Hadda","year":"2013","journal-title":"Med. Chem. Res."},{"key":"10.1016\/j.ejmech.2024.117203_bib78","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejmech.2017.02.026","article-title":"Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death","volume":"130","author":"da Silva","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib79","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112692","article-title":"The role of imidazole and benzimidazole heterocycles in Chagas disease: a review","volume":"206","author":"Beltran-Hortelano","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib80","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejmech.2015.12.017","article-title":"Pyrrole: an emerging scaffold for construction of valuable therapeutic agents","volume":"110","author":"Gholap","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib81","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3390\/ph15010035","article-title":"Thienopyrimidine: a promising Scaffold to access anti-infective agents","volume":"15","author":"Lagard\u00e8re","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.ejmech.2024.117203_bib82","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.2174\/1389557521666210210155908","article-title":"Quinoline: an attractive scaffold in drug design","volume":"21","author":"Moor","year":"2021","journal-title":"Mini Rev. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib83","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3390\/chemengineering5040073","article-title":"Recent advances on quinazoline derivatives: a potential bioactive scaffold in medicinal chemistry","volume":"5","author":"Karan","year":"2021","journal-title":"ChemEngineering"},{"key":"10.1016\/j.ejmech.2024.117203_bib84","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ejmech.2018.11.013","article-title":"Thiazole, thio and semicarbazone derivatives against tropical infective diseases: chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria","volume":"162","author":"Scarim","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib85","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1039\/D0RA06994A","article-title":"The design, synthesis, and in vitro trypanocidal and leishmanicidal activities of 1,3-thiazole and 4-thiazolidinone ester derivatives","volume":"11","author":"Haroon","year":"2021","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2024.117203_bib86","article-title":"Structural design, synthesis and anti-Trypanosoma cruzi profile of the second generation of 4-thiazolidinones chlorine derivatives","volume":"345","author":"de Oliveira Filho","year":"2021","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.ejmech.2024.117203_bib87","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2021.130014","article-title":"Synthesis, characterization and antichagasic evaluation of thiosemicarbazones prepared from chalcones and dibenzalacetones","volume":"1232","author":"da Silva","year":"2021","journal-title":"J. Mol. Struct."},{"key":"10.1016\/j.ejmech.2024.117203_bib88","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1002\/cmdc.202000331","article-title":"Dual parasiticidal activities of new phthalimides: synthesis and biological profile against trypanosoma cruzi and plasmodium falciparum","volume":"15","author":"Gomes","year":"2020","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2024.117203_bib89","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejmech.2019.07.018","article-title":"2-(phenylthio) ethylidene derivatives as anti-Trypanosoma cruzi compounds: structural design, synthesis and antiparasitic activity","volume":"180","author":"de Oliveira Cardoso","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib90","doi-asserted-by":"crossref","first-page":"10362","DOI":"10.1021\/acs.jmedchem.9b01429","article-title":"Chagas disease drug discovery: multiparametric lead optimization against trypanosoma cruzi in acylaminobenzothiazole series","volume":"62","author":"Fleau","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib91","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.3390\/molecules24173077","article-title":"Facile synthesis of a series of non-symmetric thioethers including a benzothiazole moiety and their use as efficient in vitro anti-trypanosoma cruzi agents","volume":"24","author":"Avila-Sorrosa","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2024.117203_bib92","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2019.111610","article-title":"Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease","volume":"182","author":"Monteiro","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib93","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejmech.2017.04.044","article-title":"An overview of azoles targeting sterol 14\u03b1-demethylase for antileishmanial therapy","volume":"135","author":"Emami","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib94","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1128\/AAC.48.10.3690-3696.2004","article-title":"Posaconazole is a potent inhibitor of sterol 14\u03b1-demethylation in yeasts and molds","volume":"48","author":"Munayyer","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2024.117203_bib95","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ijpddr.2011.12.002","article-title":"Recent developments in sterol 14-demethylase inhibitors for Chagas disease","volume":"2","author":"Buckner","year":"2012","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"10.1016\/j.ejmech.2024.117203_bib96","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.2174\/156802611796575902","article-title":"Sterol 14alpha-demethylase (CYP51) as a therapeutic target for human trypanosomiasis and leishmaniasis","volume":"11","author":"I Lepesheva","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib97","doi-asserted-by":"crossref","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","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2019.01.013","article-title":"Design, synthesis and molecular docking studies of novel N-arylsulfonyl-benzimidazoles with anti Trypanosoma cruzi activity","volume":"165","author":"Miana","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib99","first-page":"1","article-title":"New drug discovery strategies for the treatment of benznidazole-resistance in Trypanosoma cruzi, the causative agent of Chagas disease","author":"Murta","year":"2024","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2024.117203_bib100","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.exppara.2012.11.022","article-title":"The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives","volume":"133","author":"Charret","year":"2013","journal-title":"Exp. Parasitol."},{"key":"10.1016\/j.ejmech.2024.117203_bib101","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2020.115855","article-title":"Trypanocidal activity of new 1, 6-diphenyl-1H-pyrazolo [3, 4-b] pyridine derivatives: synthesis, in vitro and in vivo studies","volume":"29","author":"Ribeiro","year":"2021","journal-title":"Biorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib102","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1039\/D0OB00319K","article-title":"1,2-Addition to trifluoromethylated beta-enamino diketones: regioselective synthesis of trifluoromethyl-containing azomethine pyrazoles and isoxazoles","volume":"18","author":"Pianoski","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib103","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.201900213","article-title":"New aryloxy\u2010quinone derivatives with promising activity on Trypanosoma cruzi","volume":"353","author":"Espinosa\u2010Bustos","year":"2020","journal-title":"Arch. Pharm."},{"key":"10.1016\/j.ejmech.2024.117203_bib104","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1021\/tx9902082","article-title":"Role of quinones in toxicology","volume":"13","author":"Bolton","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.ejmech.2024.117203_bib105","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00044-020-02512-9","article-title":"In vitro and in silico evaluations of new aryloxy-1, 4-naphthoquinones as anti-Trypanosoma cruzi agents","volume":"29","author":"Gonz\u00e1lez","year":"2020","journal-title":"Med. Chem. Res."},{"key":"10.1016\/j.ejmech.2024.117203_bib106","article-title":"Strategies towards potent trypanocidal drugs: application of Rh-catalyzed [2+ 2+ 2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi, Biorg","volume":"28","author":"Wood","year":"2020","journal-title":"Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib107","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bioorg.2018.10.053","article-title":"Synthesis and biological evaluation of new quinoline derivatives as antileishmanial and antitrypanosomal agents","volume":"83","author":"Chanquia","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib108","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-51604-z","article-title":"Antimalarial quinoline drugs inhibit \u03b2-hematin and increase free hemin catalyzing peroxidative reactions and inhibition of cysteine proteases","volume":"9","author":"Herraiz","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2024.117203_bib109","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2021.e07024","article-title":"Synthesis and evaluation of the in vitro and in vivo antitrypanosomal activity of 2-styrylquinolines","volume":"7","author":"Espinosa","year":"2021","journal-title":"Heliyon"},{"key":"10.1016\/j.ejmech.2024.117203_bib110","first-page":"1","article-title":"Phenylpropanoid-conjugated iridoid glucosides from leaves of Morinda morindoides","author":"Hashim","year":"2022","journal-title":"J. Nat. Med."},{"key":"10.1016\/j.ejmech.2024.117203_bib111","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.fitote.2015.05.010","article-title":"Phenylpropanoids and neolignans from Smilax trinervula","volume":"104","author":"Shu","year":"2015","journal-title":"Fitoterapia"},{"key":"10.1016\/j.ejmech.2024.117203_bib112","doi-asserted-by":"crossref","first-page":"8371","DOI":"10.3390\/molecules27238371","article-title":"Role of phenylpropanoids and flavonoids in plant resistance to pests and diseases","volume":"27","author":"Ramaroson","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2024.117203_bib113","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejmech.2019.05.001","article-title":"Dehydrodieugenol B derivatives as antiparasitic agents: synthesis and biological activity against Trypanosoma cruzi","volume":"176","author":"Ferreira","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib114","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ejmech.2019.02.028","article-title":"Novel prenyloxy chalcones as potential leishmanicidal and trypanocidal agents: design, synthesis and evaluation","volume":"167","author":"Espinoza-Hicks","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib115","first-page":"1","article-title":"Synthesis and biological evaluation in vitro and in silico of N-propionyl-N\u2032-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi","author":"Delgado-Maldonado","year":"2020","journal-title":"Mol. Divers."},{"key":"10.1016\/j.ejmech.2024.117203_bib116","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2020.127491","article-title":"Expanding the scope of synthetic 1,2,4-trioxanes towards Trypanosoma cruzi and Leishmania donovani","volume":"30","author":"Medran","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2024.117203_bib117","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","year":"2019","journal-title":"Mol. Biochem. Parasitol."},{"key":"10.1016\/j.ejmech.2024.117203_bib118","series-title":"Noncanonical Interactions and Conformational Dynamics in Cargo-Pex5-Pex14 Ternary Complex for Peroxisomal Import","author":"Sonani","year":"2023"},{"key":"10.1016\/j.ejmech.2024.117203_bib119","series-title":"Analysis of the Genome of a Free-Living Amoeba Mastigamoeba Balamuthi and its Comparison with Pathogenic Entamoeba Histolytica","author":"\u017d\u00e1rsk\u00fd","year":"2020"},{"key":"10.1016\/j.ejmech.2024.117203_bib120","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1021\/acs.jcim.3c00336","article-title":"Binding site detection remastered: enabling fast, robust, and reliable binding site detection and descriptor calculation with DoGSite3","volume":"63","author":"Graef","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2024.117203_bib121","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2. 0: new docking methods, expanded force field, and python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2024.117203_bib122","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejmech.2024.117203_bib124","series-title":"Drug Designing in Discovery Studio","author":"Jejurikar","year":"2021"},{"key":"10.1016\/j.ejmech.2024.117203_bib125","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"Yuan","year":"2017","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"10.1016\/j.ejmech.2024.117203_bib126","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1021\/ci900056c","article-title":"Comparison of several molecular docking programs: pose prediction and virtual screening accuracy","volume":"49","author":"Cross","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2024.117203_bib127","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/35035189","article-title":"The twenty-first amino acid","volume":"407","author":"Atkins","year":"2000","journal-title":"Nature"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424010857?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424010857?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T16:23:37Z","timestamp":1751387017000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523424010857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":123,"alternative-id":["S0223523424010857"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.117203","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis strategies and anti-parasitic evaluation of novel compounds for chagas disease: Advancing drug discovery through structure-activity relationships","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.117203","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117203"}}