{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:39Z","timestamp":1785402219704,"version":"3.56.0"},"reference-count":152,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) from Brazil","award":["#316996\/2023-8"],"award-info":[{"award-number":["#316996\/2023-8"]}]},{"award":["#316996\/2023-8"],"award-info":[{"award-number":["#316996\/2023-8"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Coordena\u00e7\u00e3oo de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"the Coordena\u00e7\u00e3oo de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["#88887.177732\/2025-00"],"award-info":[{"award-number":["#88887.177732\/2025-00"]}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"award":["#88887.177732\/2025-00"],"award-info":[{"award-number":["#88887.177732\/2025-00"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Paraiba State Research Foundation (FAPESQ-PB) through the PRONEX program","award":["#030\/2023"],"award-info":[{"award-number":["#030\/2023"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP) through FAPESP APR","award":["#2021\/02595-8"],"award-info":[{"award-number":["#2021\/02595-8"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP) through FAPESP APR","award":["#2025\/01056-7"],"award-info":[{"award-number":["#2025\/01056-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure\u2013activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties.<\/jats:p>","DOI":"10.3390\/ph19050784","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Guanidines: Privileged Scaffolds Against Neglected Tropical Diseases: A Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-6176","authenticated-orcid":false,"given":"Luana Ribeiro","family":"dos Anjos","sequence":"first","affiliation":[{"name":"Fine Organic Chemistry Laboratory School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2403-8746","authenticated-orcid":false,"given":"Rodrigo Santos Aquino","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Federal Institute of Education, Science, and Technology os Sert\u00e3o Pernambucano (IFSert\u00e3oPE), Campus Santa Maria da Boa Vista, Santa Maria da Boa Vista 56380-000, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-680X","authenticated-orcid":false,"given":"Malu Maria Lucas","family":"dos Reis","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-4908","authenticated-orcid":false,"given":"Natalia C. S.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry, Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800-060, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit\u00f3ria Gaspar","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, Para\u00edba, Brazil"},{"name":"Post-Graduate Program in Therapeutic Innovation, Biological Sciences Center, Federal University of Pernambuco, Recife 50670-420, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-693X","authenticated-orcid":false,"given":"Eduardo Henrique","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Fine Organic Chemistry Laboratory School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-3529","authenticated-orcid":false,"given":"Klinger Antonio da Franca","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Infectious Disease Laboratory\u2014LADIC, Federal University of Parna\u00edba Delta\u2014UFDPar, Campus Ministro Reis Velloso, S\u00e3o Benedito, Parna\u00edba 64202-020, Piau\u00ed, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-0904","authenticated-orcid":false,"given":"Eduardo Maffud","family":"Cilli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry, Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800-060, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1348-8554","authenticated-orcid":false,"given":"Eduardo Ren\u00e9 P\u00e9rez","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Fine Organic Chemistry Laboratory School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-833X","authenticated-orcid":false,"given":"Francisco Jaime Bezerra","family":"Mendon\u00e7a-Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, Para\u00edba, Brazil"},{"name":"Post-Graduate Program in Therapeutic Innovation, Biological Sciences Center, Federal University of Pernambuco, Recife 50670-420, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"World Health Organization (2025). Global Report on Neglected Tropical Diseases 2025: Stronger Together, Towards 2030, WHO. Available online: https:\/\/www.who.int\/teams\/control-of-neglected-tropical-diseases\/global-report-on-neglected-tropical-diseases-2025.","DOI":"10.2471\/B09621"},{"key":"ref_2","unstructured":"World Health Organization (2021). Ending the Neglect to Attain the Sustainable Development Goals: A Roadmap for Neglected Tropical Diseases 2021\u20132030, WHO. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240010352."},{"key":"ref_3","first-page":"100022","article-title":"The burden of neglected tropical diseases: Global control programmes, research gaps and socioeconomic impact","volume":"4","author":"Ahmed","year":"2025","journal-title":"Prem. J. Public Health"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Branda, F., Smith, A., Lopez, M., Chen, H., and Kumar, S. (2024). Assessing the burden of neglected tropical diseases: Socioeconomic drivers, health infrastructure, and gaps in therapeutic resources. Viruses, 17.","DOI":"10.3390\/v17010029"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20958","DOI":"10.1038\/s41598-025-05530-y","article-title":"Global trends, health inequalities, and projections in the burden of neglected tropical diseases and malaria (1990\u20132021)","volume":"15","author":"Lin","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kioko, U., Mwangi, J., Adeyemi, O., Njeri, C., and Otieno, P. (2025). Strengthening the sustainability of neglected tropical disease programmes: Integrating into routine health service delivery. PLoS Negl. Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0012371"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.drudis.2022.04.004","article-title":"Approaches to advance drug discovery for neglected tropical diseases","volume":"27","author":"Ferreira","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115714","DOI":"10.1016\/j.ejmech.2023.115714","article-title":"Recent advances in medicinal chemistry of Neglected Tropical Diseases (NTDs)","volume":"259","author":"Zhan","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mali, S.N., Saied, E.M., dos Santos, C.B.R., and Cruz, J.N. (2025). Editorial: Medicinal chemistry for neglected tropical diseases using in-vitro, in-vivo and in silico approaches. Front. Chem., 13.","DOI":"10.3389\/fchem.2025.1689034"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"An, Q., Huang, L., Wang, C., Wang, D., and Tu, Y. (2025). New strategies to enhance the efficiency and precision of drug discovery. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1550158"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ja\u2019afaru, S.C., Uzairu, A., Hossain, S., Ullah, M.H., Sallau, M.S., Ndukwe, G.I., Ibrahim, M.T., Bayil, I., and Moin, A.T. (2024). Computer-aided discovery of novel SmDHODH inhibitors: Ligand- and structure-based approaches for schistosomiasis. PLoS Negl. Trop. Dis., 18.","DOI":"10.1371\/journal.pntd.0012453"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1016\/j.drudis.2022.05.026","article-title":"Drug repurposing: An effective strategy to accelerate contemporary drug discovery","volume":"27","author":"Zhan","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_13","first-page":"241","article-title":"Drug repurposing: A promising drug discovery strategy for infectious diseases","volume":"29","author":"Zhang","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12019","DOI":"10.2147\/DDDT.S576701","article-title":"Drug Repurposing as an Effective Drug Discovery Strategy: A Critical Review","volume":"19","author":"Wali","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.tips.2024.10.012","article-title":"Drug repurposing for neglected and zoonotic diseases","volume":"45","author":"Mentis","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101084","DOI":"10.1016\/j.jpha.2024.101084","article-title":"Exploration of innovative drug repurposing strategies for human protozoan diseases: Advances, challenges, and opportunities","volume":"15","author":"Hu","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1039\/C4CS00013G","article-title":"Guanidines: From classical approaches to efficient catalytic syntheses","volume":"43","author":"Antinolo","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2174\/138955711795049862","article-title":"Chemical and pharmacological significance of natural guanidines from marine invertebrates","volume":"11","author":"Ebada","year":"2011","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5651","DOI":"10.1002\/chem.200900508","article-title":"Solid-state structure of free base guanidine achieved at last","volume":"15","author":"Yamada","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.funbio.2016.09.001","article-title":"Antifungal activity of the cationic antimicrobial polymer polyhexamethylene guanidine hydrochloride and its mode of action","volume":"121","author":"Choi","year":"2017","journal-title":"Fungal Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106600","DOI":"10.1016\/j.bioorg.2023.106600","article-title":"Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A review","volume":"138","author":"Gomes","year":"2023","journal-title":"Bioorg. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.1021\/cr100423x","article-title":"Guanylated diamines, triamines, and polyamines: Chemistry and biological properties","volume":"111","author":"Castagnolo","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_23","first-page":"200","article-title":"Guanidine: A simple molecule with great potential: From catalysts to biocides and molecular glues","volume":"3","author":"Drozdov","year":"2021","journal-title":"Ineos Open"},{"key":"ref_24","first-page":"82","article-title":"Guanidine: Studies on the reaction with ethyl N-(2-amino-1,2-dicyanovinyl)formimidate","volume":"5","author":"Marinho","year":"2010","journal-title":"Arkivoc"},{"key":"ref_25","first-page":"1806594","article-title":"Inherent guanidine nanogels with durable antibacterial and bacterially antiadhesive properties","volume":"28","author":"Han","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39257\u221239267","DOI":"10.1021\/acsami.8b13868","article-title":"Water-insoluble polymeric guanidine derivative and application in the preparation of antibacterial coating of catheter","volume":"10","author":"Yu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113293","DOI":"10.1016\/j.ejmech.2021.113293","article-title":"Antimicrobial drugs bearing guanidine moieties: A review","volume":"216","author":"Kim","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1021\/acsmedchemlett.9b00508","article-title":"Discovery and pharmacokinetics of sulfamides and guanidines as potent human arginase 1 inhibitors","volume":"11","author":"Blaszczyk","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s00726-014-1825-9","article-title":"L-Arginine and its metabolites in kidney and cardiovascular disease","volume":"46","author":"Popolo","year":"2014","journal-title":"Amino Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s42770-025-01625-w","article-title":"Antifungal activity of guanidine compounds","volume":"56","author":"Eguiluz","year":"2025","journal-title":"Braz. J. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125470","DOI":"10.1016\/j.ijbiomac.2023.125470","article-title":"Guanidine-containing double-network silks with enhanced tensile and antibacterial property","volume":"244","author":"Baugh","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1248\/bpb.b18-00170","article-title":"Conversion of curcumin into heterocyclic compounds as potent anti-diabetic and anti-histamine agents","volume":"41","author":"Nabil","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e202200341","DOI":"10.1002\/cmdc.202200341","article-title":"Antigiardial Activity of Novel Guanidine Compounds","volume":"17","author":"Stevens","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, H.-Y., Kim, M.-S., Kim, S.-H., Joen, D., and Lee, K. (2018). Protective effects of nintedanib against polyhexamethylene guanidine phosphate-induced lung fibrosis in mice. Molecules, 23.","DOI":"10.3390\/molecules23081974"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31548","DOI":"10.1039\/D5RA05647K","article-title":"Novel Guanidine Derivatives as Mechanistic Scaffolds for Anticancer Agents: Synthesis, Characterization, DNA-Binding, and Computational Studies","volume":"15","author":"Zaman","year":"2025","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"128197","DOI":"10.1016\/j.bmcl.2021.128197","article-title":"Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea, and guanidine moieties","volume":"47","author":"Krzywik","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Pertejo, Y., Garc\u00eda-Estrada, C., Mart\u00ednez-Valladares, M., Murugesan, S., Reguera, R.M., and Bala\u00f1a-Fouce, R. (2024). Polyamine Metabolism for Drug Intervention in Trypanosomatids. Pathogens, 13.","DOI":"10.3390\/pathogens13010079"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113545","DOI":"10.1016\/j.ejmech.2021.113545","article-title":"Synthesis, in vitro antiprotozoal activity, molecular docking and molecular dynamics studies of some new monocationic guanidinobenzimidazoles","volume":"221","author":"Doganc","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1517\/13543776.2013.788645","article-title":"Biological activities of guanidine compounds, 2008\u20142012 update","volume":"23","author":"Balewski","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1016\/j.ejmech.2008.02.008","article-title":"Novel linear triaryl guanidines, N-substituted guanidines and potential prodrugs as antiprotozoal agents","volume":"43","author":"Arafa","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.2174\/15680266113139990126","article-title":"Thiourea and guanidine derivatives as antimalarial and antimicrobial agents","volume":"13","author":"Mishra","year":"2013","journal-title":"Curr. To. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1021\/acsinfecdis.1c00001","article-title":"Robenidine Analogues are Potent Antimalarials in Drug-Resistant Plasmodium falciparum","volume":"7","author":"Krollenbrock","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100546","DOI":"10.1016\/j.ijpddr.2024.100546","article-title":"Robenidine derivatives as potential antischistosomal drug candidates","volume":"25","author":"Lotz","year":"2024","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e1900068","DOI":"10.1002\/ardp.201900068","article-title":"Synthesis and mycobacterial evaluation of 5-substituted-6-acetyl-2-amino-7-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-one derivatives","volume":"352","author":"Agre","year":"2019","journal-title":"Arch. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1128\/AAC.49.8.3463-3467.2005","article-title":"Triazine Inhibits Toxoplasma gondii Tachyzoites In Vitro and In Vivo","volume":"49","author":"Mui","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mui, E.J., Schiehser, G.A., Milhous, W.K., Hsu, H., Roberts, C.W., Kirisits, M., Muench, S., Rice, D., Dubey, J.P., and Fowble, J.W. (2008). Novel Triazine JPC-2067-B Inhibits Toxoplasma gondii In Vitro and In Vivo. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000190"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1021\/jm7009364","article-title":"Multi-target-directed ligands to combat neurodegenerative diseases","volume":"51","author":"Cavalli","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_48","unstructured":"WHO\u2014World Health Organization (2025, December 22). Chagas Disease (American Trypanosomiasis). Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs340\/en\/."},{"key":"ref_49","unstructured":"WHO\u2014World Health Organization (2025, December 22). Chagas Disease (Also Known as American Trypanosomiasis). Available online: http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2174\/187152507781058726","article-title":"Natural products to anti-trypanosomal drugs: An overview of new drug prototypes for american trypanosomiasis","volume":"5","author":"Tempone","year":"2007","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100507","DOI":"10.1016\/j.cpcardiol.2019.100507","article-title":"Chagas disease: Chronic chagas cardiomyopathy","volume":"46","author":"Stewart","year":"2021","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"Molina","year":"2018","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10369","DOI":"10.1021\/cr400552x","article-title":"Fruitful decade for antileishmanial compounds from 2002 to late 2011","volume":"114","author":"Hussain","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1590\/0074-0276108022013022","article-title":"Certifying the interruption of chagas disease transmission by native vectors: Cui bono?","volume":"108","author":"Diotaiuti","year":"2013","journal-title":"Mem. Inst. Oswaldo Cruz."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1186\/s13071-015-1211-9","article-title":"Inheritance and heritability of deltamethrin resistance under laboratory conditions of Triatoma infestans from Bolivia","volume":"8","author":"Gomez","year":"2015","journal-title":"Parasit. Vectors."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.biochi.2019.08.015","article-title":"Evaluation of clan CD C11 peptidase PNT1 and other Leishmania mexicana cysteine peptidases as potential drug targets","volume":"166","author":"Grewal","year":"2019","journal-title":"Biochimie"},{"key":"ref_57","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":"Alcolea","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102958","DOI":"10.1016\/j.arcmed.2024.102958","article-title":"Repositioning FDA-approved drug against chagas disease and cutaneous leishmaniosis by structure-based virtual screening","volume":"55","author":"Rivera","year":"2024","journal-title":"Arch. Med. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10062","DOI":"10.1073\/pnas.96.18.10062","article-title":"Crystal structure of triosephosphate isomerase from Trypanosoma cruzi in hexane","volume":"96","author":"Gao","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.bpj.2015.06.031","article-title":"How an inhibitor bound to subunit interface alters triosephosphate isomerase dynamics","volume":"109","author":"Kurkcuoglu","year":"2015","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ju\u00e1rez-Saldivar, A., Schroeder, M., Salentin, S., Haupt, V.J., Saavedra, E., V\u00e1zquez, C., Reyes-Espinosa, F., Herrera-Mayorga, V., Villalobos-Rocha, J.C., and Garc\u00eda-P\u00e9rez, C.A. (2020). Computational drug repositioning for chagas disease using protein-ligand interaction profiling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124270"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.abb.2013.03.015","article-title":"Crystal structure of arginase from Leishmania mexicana and implications for the inhibition of polyamine biosynthesis in parasitic infections","volume":"535","author":"Ullman","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1111\/j.1476-5381.2009.00374.x","article-title":"Arginase: A key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives","volume":"158","author":"Maarsingh","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3360001","article-title":"Arginine metabolism: Nitric oxide and beyond","volume":"336","author":"Wu","year":"1998","journal-title":"Biochem. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"H651","DOI":"10.1152\/ajpheart.00755.2012","article-title":"Insights into the arginine paradox: Evidence against the importance of subcellular location of arginase and eNOS","volume":"305","author":"Elms","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1016\/j.bmc.2018.06.015","article-title":"Rational design of novel irreversible inhibitors for human arginase","volume":"26","author":"Guo","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1021\/jm058190h","article-title":"Synthesis, DNA affinity, and antiprotozoal activity of fused ring dicationic compounds and their prodrugs","volume":"48","author":"Arafa","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1517\/13543770903216675","article-title":"Biological activities of guanidine compounds","volume":"19","author":"Saczewski","year":"2009","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1021\/acs.jnatprod.5b00070","article-title":"Anti-parasitic guanidine and pyrimidine alkaloids from the marine sponge Monanchora arbuscula","volume":"78","author":"Santos","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1021\/acs.jnatprod.6b00256","article-title":"Analogues of marine guanidine alkaloids are in vitro effective against Trypanosoma cruzi and selectively eliminate Leishmania (L.) infantum intracellular amastigotes","volume":"79","author":"Martins","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Alba-Alvarado, M.C., Torres-Guti\u00e9rrez, E., Reynoso-Ducoing, O.A., Zenteno-Galindo, E., Cabrera-Bravo, M., Guevara-G\u00f3mez, Y., Salazar-Schettino, P.M., Rivera-Fern\u00e1ndez, N., and Bucio-Torres, M.I. (2023). Immunopathological mechanisms underlying cardiac damage in chagas disease. Pathogens, 12.","DOI":"10.3390\/pathogens12020335"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"qiaf134","DOI":"10.1093\/jleuko\/qiaf134","article-title":"Metformin improves CD8+ T cell responses and parasitemia control via macrophage modulation during Trypanosoma cruzi infection","volume":"117","author":"Baigorri","year":"2025","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Andrade, D.V., Gollob, K.J., and Dutra, W.O. (2014). Acute chagas disease: New global challenges for an old neglected disease. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003010"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/mve.12206","article-title":"Assessment of the anti-feeding and insecticidal effects of the combination of dinotefuran, permethrin and pyriproxyfen (Vectra\u00ae 3D) against Triatoma infestans on rats","volume":"31","author":"Tahir","year":"2017","journal-title":"Med. Vet. Entomol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1179\/2047773213Y.0000000105","article-title":"A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis","volume":"107","author":"Babokhov","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human african trypanosomiasis","volume":"390","author":"Cecchi","year":"2017","journal-title":"Lancet"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1016\/j.bmc.2016.08.036","article-title":"Synthesis and biological evaluation of N-cyanoalkyl-, N-aminoalkyl-, and N-gunidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents","volume":"24","author":"Sola","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Pereira, M.A., and Santos-Gomes, G. (2022). Parasitic infection and immunity\u2014A special biomedicines issue. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102547"},{"key":"ref_79","unstructured":"WHO\u2014World Health Organization (2026, February 03). Trypanosomiasis, Human African (Sleeping Sickness). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/trypanosomiasis-human-african-(sleeping-sickness)."},{"key":"ref_80","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":"ref_81","doi-asserted-by":"crossref","unstructured":"Kasozi, K.I., Macleod, E.T., Ntulume, I., and Welburn, S.C. (2022). An update on african trypanocide pharmaceutics and resistance. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.828111"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.ejmech.2015.07.013","article-title":"Lowering the pKa of a bisimidazoline lead with halogen atoms results in improved activity and selectivity against Trypanosoma brucei in vitro","volume":"101","author":"Ebiloma","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"116162","DOI":"10.1016\/j.ejmech.2024.116162","article-title":"Novel aroyl guanidine anti-trypanosomal compounds that exert opposing effects on parasite energy metabolism","volume":"268","author":"Varghese","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1016\/j.bmc.2014.12.066","article-title":"Evaluation of histone deacetylase inhibitors (HDACi) as therapeutic leads for human African trypanosomiasis (HAT)","volume":"23","author":"Carrillo","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1128\/AAC.02309-13","article-title":"In vitro and in vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness","volume":"58","author":"Wenzler","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1021\/jm301614w","article-title":"Aminoalkyl derivatives of guanidine diaromatic minor groove binders with antiprotozoal activity","volume":"56","author":"McKeever","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1042\/bse0510063","article-title":"Folate metabolic pathways in Leishmania","volume":"51","author":"Vickers","year":"2011","journal-title":"Essays Biochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1021\/acsinfecdis.4c00113","article-title":"Identification of innovative folate inhibitors leveraging the amino dihydrotriazine motif from cycloguanil for their potential as anti-Trypanosoma brucei agents","volume":"10","author":"Francesconi","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1021\/acsinfecdis.8b00358","article-title":"Structural insights into the development of cycloguanil derivatives as Trypanosoma brucei pteridine-reductase-1 inhibitors","volume":"5","author":"Landi","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1016\/j.bmc.2016.06.047","article-title":"Synthesis and potent antiprotozoal activity of mono\/di amidino 2-anilinobenzimidazoles versus Plasmodium falciparum and Trypanosoma brucei rhodesiense","volume":"24","author":"Karaaslan","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.biochi.2008.02.017","article-title":"Antiparasitic compounds that target DNA","volume":"90","author":"Wilson","year":"2008","journal-title":"Biochimie"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8378","DOI":"10.1093\/nar\/gkx521","article-title":"Functional and structural analysis of AT-specific minor groove binders that disrupt DNA-protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast","volume":"45","author":"Millan","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_93","unstructured":"(2026, March 20). Leishmaniasis: Epidemiological Report for the Americas. No. 13, December 2024. Available online: https:\/\/iris.paho.org\/handle\/10665.2\/63165."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.36557\/2674-8169.2024v6n9p3501-3518","article-title":"Desafios da terap\u00eautica da leishmaniose: Limita\u00e7\u00f5es atuais e perspectivas futuras","volume":"6","author":"Viana","year":"2024","journal-title":"Braz. J. Implantol. Health Sci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Firdessa, R., Good, L., Amstalden, M.C., Chindera, K., Kamaruzzaman, N.F., Schultheis, M., R\u00f6ger, B., Hecht, N., Oelschlaeger, T.A., and Meinel, L. (2015). Pathogen-and host-directed antileishmanial effects mediated by polyhexanide (PHMB). PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004041"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1021\/acsmedchemlett.7b00045","article-title":"Identification of a hit series of antileishmanial compounds through the use of mixture-based libraries","volume":"8","author":"Giulianotti","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ijantimicag.2019.07.013","article-title":"Development of a target-free high-throughput screening platform for the discovery of antileishmanial compounds","volume":"54","author":"Corman","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ferreira, R.A.A., Junior, C.D.O.R., Martinez, P.D.G., Koovits, P.J., Soares, B.M., Ferreira, L.L.G., Michelan-Duarte, S., Chelucci, R.C., Andricopulo, A.D., and Galuppo, M.K. (2021). 2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009196"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11495","DOI":"10.1080\/07391102.2021.1959403","article-title":"Exploring the antileishmanial activity of N 1, N 2-disubstituted-benzoylguanidines: Synthesis and molecular modeling studies","volume":"40","author":"Bortoleti","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejmech.2019.03.032","article-title":"N, N\u2032, N \u2033-trisubstituted guanidines: Synthesis, characterization and evaluation of their leishmanicidal activity","volume":"171","author":"Passianoto","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"114165","DOI":"10.1016\/j.ejmech.2022.114165","article-title":"N6-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","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/1573406417666210216154428","article-title":"Synthesis, antileishmanial activity and in silico studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) against Leishmania chagasi amastigotes","volume":"18","author":"Rodrigues","year":"2022","journal-title":"Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"116256","DOI":"10.1016\/j.ejmech.2024.116256","article-title":"Hit-to-lead optimization of 2-aminoquinazolines as anti-microbial agents against Leishmania donovani","volume":"269","author":"Das","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Moreira, V.P., da Silva Mela, M.F., dos Anjos, L.R., Saraiva, L.F., Arenas Vel\u00e1squez, A.M., Kalaba, P., Fabisikov\u00e1, A., Clementino, L.D.C., Aufy, M., and Studenik, C. (2022). Novel Selective and Low-Toxic Inhibitor of Lm CPB2. 8\u0394CTE (CPB) One Important Cysteine Protease for Leishmania Virulence. Biomolecules, 12.","DOI":"10.3390\/biom12121903"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Almeida, F.S., Moreira, V.P., Silva, E.D.S., Cardoso, L.L., de Sousa Palmeira, P.H., Cavalcante-Silva, L.H.A., de Ara\u00fajo, D.A.M., do Amaral, I.P.G., Gonz\u00e1lez, E.R.P., and Keesen, T.S.L. (2023). Leishmanicidal activity of guanidine derivatives against Leishmania infantum. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8030141"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"dos Anjos, L.R., de Souza, V.M.R., Machado, Y.A.A., Partite, V.M., Aufy, M., Dias Lopes, G., Studenik, C., Alves, C.R., Lubec, G., and Gonz\u00e1lez, E.R.P. (2023). Evidence of guanidines potential against Leishmania (Viannia) braziliensis: Exploring in vitro effectiveness, toxicities and of innate immunity response effects. Biomolecules, 14.","DOI":"10.3390\/biom14010026"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"34008","DOI":"10.1021\/acsomega.3c04878","article-title":"Development of new leishmanicidal compounds via bioconjugation of antimicrobial peptides and antileishmanial guanidines","volume":"8","author":"Costa","year":"2023","journal-title":"ACS Omega"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"de Souza, J.V.M., Costa, N.C.S., Brasil, M.C.O.A., dos Anjos, L.R., de Menezes, R.P.B., Zampieri, E.H., de Lima, J.S., Velasquez, A.M.A., Scotti, L., and Scotti, M.T. (2025). Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules. Molecules, 30.","DOI":"10.3390\/molecules30020264"},{"key":"ref_109","first-page":"117651","article-title":"Study of the Antileishmanial Activity of Novel Guanidine and Hybrid Acridine\u2013Guanidine Compounds","volume":"1","author":"Fabisikova","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"133899","DOI":"10.1016\/j.molstruc.2022.133899","article-title":"Synthesis, characterization, anti-tuberculosis activity and molecular modeling studies of thiourea derivatives bearing aminoguanidine moiety","volume":"1270","author":"Tapera","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e3428","DOI":"10.1002\/psc.3428","article-title":"Discovery, synthesis, and optimization of teixobactin, a novel antibiotic without detectable bacterial resistance","volume":"28","author":"Qi","year":"2022","journal-title":"J. Pept. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature14098","article-title":"A new antibiotic kills pathogens without detectable resistance","volume":"517","author":"Ling","year":"2015","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1016\/j.bmc.2012.01.041","article-title":"Synthesis and investigation of the antimycobacterial activity of guanidinium-modified compounds","volume":"20","author":"Mourer","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.1016\/j.bmc.2015.07.053","article-title":"Guanidinium compounds with sub-micromolar activities against Mycobacterium tuberculosis: Synthesis, characterization and biological evaluations","volume":"23","author":"Mourer","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.bmcl.2014.02.012","article-title":"4,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine containing phenothiazines as antitubercular agents","volume":"24","author":"Siddiqui","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejmech.2018.11.054","article-title":"Design and synthesis of novel pyrimidine derivatives as potent antitubercular agents","volume":"163","author":"Liu","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1007\/s11172-024-4286-7","article-title":"3,6-Disubstituted derivatives of 1,2,4,5-tetrazine with pyridinyl amidine moieties and condensed systems on their basis: Synthesis, docking, and antibacterial activity","volume":"73","author":"Ishmetova","year":"2024","journal-title":"Russ. Chem. Bull."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"112035","DOI":"10.1016\/j.ejmech.2020.112035","article-title":"Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors","volume":"188","author":"Krishna","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1134\/S1068162023020206","article-title":"Isolation, functionalization, in silico investigation, and synthesis of 1,8-cineole analog as antitubercular agent targeting InhA","volume":"49","author":"Sabarees","year":"2023","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_120","first-page":"1398","article-title":"Synthesis, in vitro antiproliferative and anti-Mycobacterium tuberculosis activities of novel \u03b2-carboline derivatives","volume":"27","author":"Moreira","year":"2016","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1128\/AAC.01683-15","article-title":"Guanabenz Repurposed as an Antiparasitic with Activity against Acute and Latent Toxoplasmosis","volume":"59","author":"Benmerzouga","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1007\/s00436-023-07936-x","article-title":"Sulfadiazine analogs: Anti-Toxoplasma in vitro study of sulfonamide triazoles","volume":"122","author":"Arafa","year":"2023","journal-title":"Parasitol. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1021\/acs.jmedchem.8b01754","article-title":"Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis","volume":"62","author":"Hopper","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1021\/acsmedchemlett.6b00328","article-title":"Discovery of potent and selective leads against Toxoplasma gondii dihydrofolate reductase via structure-based design","volume":"7","author":"Welsch","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Singh, D., Sleda, M.A., Pandey, A., Malwal, S.R., Chen, Y., Zhou, R., Adewole, F., Sadowska, K., Onajole, O.K., and Moreno, S.N.J. (2025). Activity of Carbazole, Aminoguanidine and Diamine Anti-infectives against Toxoplasma gondii. bioRxiv, status (preprint).","DOI":"10.1101\/2025.02.15.638445"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"18941","DOI":"10.1038\/s41598-019-55379-1","article-title":"Identification of a Phenylthiazole Small Molecule with Dual Antifungal and Antibiofilm Activity Against Candida albicans and Candida auris","volume":"9","author":"Mohammad","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"115227","DOI":"10.1016\/j.ejmech.2023.115227","article-title":"N-sulfonyl peptide-hybrids as a new class of dengue virus protease inhibitors","volume":"251","author":"Behrouz","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ejmech.2016.04.008","article-title":"Progress and prospects on dengue virus protease inhibitors","volume":"117","author":"Timiri","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.antiviral.2015.03.010","article-title":"Antiviral activities of 15 dengue NS2B\u2013NS3 protease inhibitors using a human cell-based assay","volume":"118","author":"Chu","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"116415","DOI":"10.1016\/j.bmc.2021.116415","article-title":"A short survey of dengue protease inhibitor development in the past 6 years (2015\u20132020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases","volume":"49","author":"Murtuja","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e00097124","DOI":"10.1590\/0102-311xpt097124","article-title":"Elementos de desinforma\u00e7\u00e3o na percep\u00e7\u00e3o p\u00fablica sobre a vacina contra a dengue no Brasil","volume":"41","author":"Oliveira","year":"2025","journal-title":"Cad. Sa\u00fade P\u00fablica"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"101772","DOI":"10.1016\/j.jbc.2022.101772","article-title":"Structure-guided affinity maturation of antibody against dengue virus envelope protein","volume":"298","author":"Sarker","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2017.08.003","article-title":"Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review","volume":"40","author":"Campbell","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Halabitska, I., Petakh, P., Lushchak, O., Kamyshna, I., and Oksenych, V. (2024). Metformin in antiviral therapy: Evidence and perspectives. Front. Pharmacol., 15.","DOI":"10.20944\/preprints202412.0808.v1"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"129533","DOI":"10.1016\/j.bbagen.2020.129533","article-title":"Metformin attenuates adhesion between cancer and endothelial cells via glycocalyx recovery","volume":"1864","author":"Kloska","year":"2020","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1038\/s41598-018-21612-6","article-title":"Metformin use and severe dengue in diabetic adults","volume":"8","author":"Htun","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1038\/s41598-021-87707-9","article-title":"The antiviral effect of metformin on Zika and dengue virus infection","volume":"11","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.5694\/j.1326-5377.1972.tb108049.x","article-title":"Treatment of dengue fever with Vironil","volume":"1","year":"1972","journal-title":"Med. J. Aust."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"113726","DOI":"10.1016\/j.ejmech.2021.113726","article-title":"Biguanide drugs: Past success stories and promising future for drug discovery","volume":"224","author":"Grytsai","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_140","first-page":"484","article-title":"Dengue virus entry\/fusion inhibition by small bioactive molecules: A critical review","volume":"23","author":"Naresh","year":"2022","journal-title":"Curr. Drug Targets"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejmech.2019.05.025","article-title":"Synthesis and structure\u2013activity relationships of flaviviral protease inhibitors","volume":"176","author":"Sundermann","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4945","DOI":"10.2174\/0929867326666181204155336","article-title":"Discovery of dengue virus inhibitors","volume":"27","author":"Abdullah","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1080\/14756366.2017.1306521","article-title":"Effects of NS2B\u2013NS3 protease and furin inhibition on West Nile and dengue virus replication","volume":"32","author":"Kouretova","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/cmdc.202000237","article-title":"Structure-based macrocyclization of substrate analogue NS2B\u2013NS3 protease inhibitors of Zika, West Nile and dengue viruses","volume":"15","author":"Braun","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_145","first-page":"1","article-title":"Barriers in the control of schistosomiasis with mass distribution of praziquantel in Bauchi State, Nigeria: A phenomenological study","volume":"4","author":"Adeyemo","year":"2025","journal-title":"Discov. Health Syst."},{"key":"ref_146","first-page":"e03077","article-title":"Understanding schistosomiasis transmission: A systematic review of mathematical models","volume":"30","author":"Abokwara","year":"2025","journal-title":"Sci. Afr."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0140-6736(24)02814-9","article-title":"Human schistosomiasis","volume":"405","author":"Buonfrate","year":"2025","journal-title":"Lancet"},{"key":"ref_148","first-page":"101","article-title":"A high-fat diet and schistosomiasis mansoni cause histological changes in mice livers","volume":"21","author":"Filomeno","year":"2022","journal-title":"Braz. J. Health Biomed. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Maillard, D., Spangenberg, T., and Sylla, Y. (2026). From small molecule to drug product: The chemical journey of praziquantel. Praziquantel, Springer.","DOI":"10.1007\/978-3-031-97397-0_4"},{"key":"ref_150","first-page":"897","article-title":"Synthesis of fluorine and phosphorus compounds bearing an amino pyrimidine-substituted pyrazolo[3,4-d]pyrimidine moiety as molluscicidal agents against some snails","volume":"41","year":"2019","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chemosphere.2018.10.035","article-title":"Molluscicidal activity of polyhexamethylene biguanide hydrochloride on Biomphalaria glabrata","volume":"216","author":"Santos","year":"2019","journal-title":"Chemosphere"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"205","DOI":"10.47665\/tb.38.2.059","article-title":"Adjuvant effect of metformin with praziquantel in Schistosoma mansoni-infected mice","volume":"38","author":"Salama","year":"2021","journal-title":"Trop. Biomed."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:21:37Z","timestamp":1779456097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":152,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ph19050784"],"URL":"https:\/\/doi.org\/10.3390\/ph19050784","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]}}}