{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:46:50Z","timestamp":1782697610163,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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":[[2026,6,26]]},"abstract":"<jats:p>\n                    The Trypanosomatidae family, which includes\n                    <jats:italic>Trypanosoma<\/jats:italic>\n                    and\n                    <jats:italic>Leishmania<\/jats:italic>\n                    species, is responsible for several neglected tropical diseases. The limitations of current therapies highlight the urgent need for novel therapeutic strategies. Here, we report the design and synthesis of 43 new hybrid molecules that combine isatin and thiazole scaffolds, which were evaluated for their in vitro anti\u2010Trypanosomatidae activity and subjected to in silico analyses. In the anti\u2010\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    assays, 12 compounds displayed EC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 1.30 to 3.14\u2009\u00b5M, comparable to that of benznidazole (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20093.17\u2009\u00b5M). In the leishmanicidal assays, against the promastigote form of\n                    <jats:italic>Leishmania amazonensis<\/jats:italic>\n                    , 36 compounds exhibited EC\n                    <jats:sub>50<\/jats:sub>\n                    values lower than miltefosine (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200926.74\u2009\u00b5M), with compounds 8 and 10 emerging as the most potent (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.40\u2009\u00b5M). However, none surpassed miltefosine against the amastigote form of\n                    <jats:italic>Leishmania infantum or L. amazonensis<\/jats:italic>\n                    . The compounds exhibited cytotoxicity toward RAW 264.7 macrophages and L929 fibroblasts. In silico predictions indicated that all synthesized compounds presented favorable bioavailability scores, drug\u2010likeness profiles, and physicochemical stability. Moreover, molecular and electronic structure analyses revealed a moderate, positive, and statistically significant correlation (\n                    <jats:italic>\u03c1<\/jats:italic>\n                    \u2009=\u20090.50,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) with trypanothione reductase, suggesting this enzyme as a potential biological target in\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500954","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:49:47Z","timestamp":1781840987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the Antitrypanosomatid Activity of Thiazolyl\u2013Isatins: Synthesis, Biological Evaluation, and Electronic Structure Analysis Using the Semiempirical GFN2\u2010xTB Method"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4233-4066","authenticated-orcid":false,"given":"Lucas Manoel","family":"da Silva Sousa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-3705","authenticated-orcid":false,"given":"Luiz Alberto","family":"Barros Freitas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-5790","authenticated-orcid":false,"given":"Vanessa Gouveia","family":"de Melo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0759-8335","authenticated-orcid":false,"given":"Janine Siqueira","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-5653","authenticated-orcid":false,"given":"Paulo Andr\u00e9 Teixeira","family":"de Moraes Gomes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-8992","authenticated-orcid":false,"given":"Beatriz de F\u00e1tima Maia","family":"de Santana","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7397-9744","authenticated-orcid":false,"given":"Vanessa Soares","family":"Sales","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0569-8638","authenticated-orcid":false,"given":"Jos\u00e9 Leandro","family":"de Albuquerque Barros","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-2555","authenticated-orcid":false,"given":"Policarpo Ademar","family":"Sales Junior","sequence":"additional","affiliation":[{"name":"Aggeu Magalh\u00e3es Institute Oswaldo Cruz Foundation  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-7360","authenticated-orcid":false,"given":"Val\u00e9ria R\u00eago","family":"Alves Pereira","sequence":"additional","affiliation":[{"name":"Aggeu Magalh\u00e3es Institute Oswaldo Cruz Foundation  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 Center of Health Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182018000951"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460913.2024.2431417"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182023000422"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006052"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0RA06994A"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117191"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116059"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-024-03621-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2025.127475"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109561"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110954"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.11.2592"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762010000200022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2019.105732"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2011.09.006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci200227u"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b01176"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27072163"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11020054"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/096032719401301209"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2021.106459"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2023.152779"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035085"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1017\/pao.2018.15"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11091052"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180820666230224112505"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjac.2023.100330"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2016.02.028"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(96)00423-1"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc9800071"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm015507e"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000942e"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52764-8"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100950p"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500954","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500954","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500954","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:42:56Z","timestamp":1782697376000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,6,26]]}},"alternative-id":["10.1002\/cmdc.202500954"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500954","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"assertion":[{"value":"2025-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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