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It is a deadly condition claiming the lives of millions of individuals annually, with no therapeutic treatment available to date. The management of diabetes is thus limited to symptomatic relief by glycemic control. Furthermore, the geographical overlap of diabetes and neglected tropical diseases (NTDs) is of concern, as diabetes is known to increase infection susceptibility and severity. In contrast, diabetes\u2010infection comorbidity can negatively affect treatment responses. Leishmaniasis ranks among the top 10 NTDs. Its current therapeutic treatment relies on a handful of drugs that are marred with two main shortcomings: toxicity and reduced efficacy due to pathogenic resistance. Hence, there is a pressing need for new, effective antileishmanial therapeutics. There is evidence of rising cases of leishmaniasis\u2010diabetes co\u2010infection, which may require the use of dual\u2010active therapeutics to curb them. In search of new effective antileishmanial agents with potential for dual use, we evaluated in vitro the antileishmanial and antidiabetic activities of a series of arylidenes derived from hydantoin, glitazone, and rhodanine scaffolds using phenotypic assays, some of which had previously been investigated for antidiabetic potential. Additionally, the antitrypanosomal potential of these compounds was also considered due to the taxonomic relation between <jats:italic>Leishmania<\/jats:italic> and <jats:italic>Trypanosoma<\/jats:italic> spp. and reported concerns of Chagas disease and human African trypanosomiasis\u2010diabetes comorbidities. Three leishmanicidal early leads with submicromolar activity were uncovered, but no antitrypanosomal or dual leishmaniasis\u2010diabetes active hits were identified.<\/jats:p>","DOI":"10.1002\/ddr.70125","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T10:25:02Z","timestamp":1752488702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vitro Leishmanicidal Efficacy of Synthesized Arylidene Analogues of Glitazone"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-5532","authenticated-orcid":false,"given":"Janine","family":"Aucamp","sequence":"first","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen), Faculty of Health Sciences North\u2010West University Potchefstroom North West Province South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-7489","authenticated-orcid":false,"given":"Helena D.","family":"Janse van Rensburg","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen), Faculty of Health Sciences North\u2010West University Potchefstroom North West Province South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7124-9124","authenticated-orcid":false,"given":"Simon S.","family":"Mnyakeni\u2010Moleele","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Venda Thohoyandou Limpopo Province 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, Inada Obihiro Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0551","authenticated-orcid":false,"given":"David D.","family":"N'Da","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (Pharmacen), Faculty of Health Sciences North\u2010West University Potchefstroom North West Province South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1934578X1300800906"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.05.017"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2470110"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.94253"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0663-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.12.066"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/20477724.2020.1754655"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(16)30081-x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-108-6_5"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.04.045"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109773"},{"key":"e_1_2_11_16_1","unstructured":"DNDi. 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