{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:28:16Z","timestamp":1787772496972,"version":"build-2784847793"},"reference-count":62,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:p>\n                    Chagas disease and leishmaniasis are neglected tropical diseases caused by the trypanosomatid protozoa\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    and\n                    <jats:italic>Leishmania<\/jats:italic>\n                    spp., respectively. Currently available treatments are often insufficiently effective and lack the characteristics of ideal therapeutics. Here we report the design, synthesis, and antitrypanosomatid evaluation of 20 novel hybrid compounds incorporating pyridine, thiazole, and thiosemicarbazone scaffolds. All compounds were tested against trypomastigote and amastigote forms of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    , as well as promastigote and amastigote forms of\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    and\n                    <jats:italic>L. amazonensis<\/jats:italic>\n                    . Cytotoxicity was assessed in L929 fibroblasts and RAW 264.7 macrophages. Compound 8 emerged as the lead, displaying an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 1.0\u2009\u00b5M against\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    and a selectivity index of 52.8. Despite its potent in vitro activity, Compound 8 exhibited poor in vivo efficacy when administered orally at 150\u2009mg\/kg\/day. In silico analyses predicted strong binding to cruzain, alongside favorable bioavailability, drug\u2010likeness, and chemical stability. Against\n                    <jats:italic>Leishmania<\/jats:italic>\n                    species, Compound 8 demonstrated selectivity comparable to miltefosine against\n                    <jats:italic>L. amazonensis<\/jats:italic>\n                    amastigotes. Collectively, these findings identify a novel chemical scaffold with promising antitrypanosomatid potential that warrants further optimization to improve in vivo performance.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70443","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:00:57Z","timestamp":1787299257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyridyl\u2010Thiazole\u2010Thiosemicarbazones as Antitrypanosomatidae Agents: Design, Synthesis, and In Silico Profiling"],"prefix":"10.1002","volume":"21","author":[{"given":"Anderson Jos\u00e9 Firmino Santos da","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiane Santiago da Cruz","family":"Olimpio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Manoel da Silva","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella Leite","family":"Brondani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tacylla Lima","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W\u00e9llyda Belmira de Lira","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1li Tereza Capistrano","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Zaldini","family":"Hernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Policarpo Ademar Sales","family":"Junior","sequence":"additional","affiliation":[{"name":"Aggeu Magalh\u00e3es Institute Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ)  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria R\u00eago Alves","family":"Pereira","sequence":"additional","affiliation":[{"name":"Aggeu Magalh\u00e3es Institute Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ)  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-2292","authenticated-orcid":false,"given":"Ana Cristina Lima","family":"Leite","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Health Sciences Centre Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2022.111510"},{"key":"e_1_2_9_3_1","unstructured":"Chagas Disease \u201cCenters for 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