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Nitroheterocycles continue to be clinically relevant due to their redox activation within parasites, and the 1,2,3\u2010triazole linker offers a modular approach by enabling systematic variation of substituents, thereby allowing controlled modulation of physicochemical and biological properties. Accordingly, this study investigated a new library of 5\u2010nitroimidazole\u20101,2,3\u2010triazole hybrids and evaluated substituent\u2010dependent effects on their antiparasitic activity. A series of 5\u2010nitroimidazole\u20101,2,3\u2010triazole hybrids was synthesised via copper(I)\u2010catalysed azide\u2013alkyne cycloaddition and evaluated in vitro for their antileishmanial and antitrypanosomal activity, alongside cytotoxicity profiling. Most compounds exhibited low toxicity against mammalian cell lines. No antileishmanial hit was uncovered. In the trypanosome panel,\n                    <jats:bold>3j<\/jats:bold>\n                    demonstrated selective micromolar inhibition against\n                    <jats:italic>Trypanosoma congolense<\/jats:italic>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 6.38\u2009\u00b1\u20091.03 \u00b5M, SI = 48); hence, it was identified as a trypanocidal hit.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70375","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:05:27Z","timestamp":1784095527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Probing 5\u2010Nitroimidazole\u2010Triazole Hybrids as Potential Anti\u2010Kinetoplastid Agents: Synthesis and In Vitro Efficacy"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8948-6438","authenticated-orcid":false,"given":"Liandi","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen) Faculty of Health Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon D.","family":"Badenhorst","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen) Faculty of Health Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-5532","authenticated-orcid":false,"given":"Janine","family":"Aucamp","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen) Faculty of Health Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5809-8811","authenticated-orcid":false,"given":"Keisuke","family":"Suganuma","sequence":"additional","affiliation":[{"name":"National Research Center for Protozoan Diseases Obihiro University of Agriculture and Veterinary Medicine  Obihiro Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0551","authenticated-orcid":false,"given":"David D.","family":"N\u2019Da","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen) Faculty of Health Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens14090844"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18091415"},{"key":"e_1_2_13_4_1","unstructured":"WHO Neglected Tropical Diseases 2025 accessed December 3 2025 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