{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:57:48Z","timestamp":1790279868526,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009391","name":"Kafkas University Scientific Research Projects Coordination Unit","doi-asserted-by":"publisher","award":["2025-TS-57"],"award-info":[{"award-number":["2025-TS-57"]}],"id":[{"id":"10.13039\/501100009391","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025-TS-57"],"award-info":[{"award-number":["2025-TS-57"]}],"id":[{"id":"https:\/\/ror.org\/04v302n28","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The present study aimed to design, synthesize, and evaluate a new series of thieno[3,2-d]pyrimidin-4(3H)-one-based Schiff bases as potential antileishmanial agents against Leishmania major (L. major). A series of twenty thieno[3,2-d]pyrimidine Schiff base derivatives were synthesized and characterized using FTIR, NMR, and HRMS techniques. Their antipromastigote activities were evaluated in vitro against L. major, while cytotoxic effects were assessed on HUVECs to determine selectivity indices. The most active compound was further investigated using molecular docking against several L. major proteins. Among the tested compounds, compound 12, bearing a 2-hydroxy-5-bromophenyl moiety, exhibited the most potent activity against L. major promastigotes with an IC50 value of 13.7 \u00b5M, along with a favorable selectivity index (SI = 17.5), outperforming the reference drug miltefosine (IC50 = 31 \u00b5M and SI = 0.2). Docking studies demonstrated that compound 12 showed the strongest binding affinity toward phosphodiesterase B1, supported by a docking score of \u22129.042 kcal\/mol and an MM-GBSA value of \u221267.21 kcal\/mol. This study highlights thieno[3,2-d]pyrimidin-4(3H)-one as a promising scaffold in the context of in vitro antileishmanial screening and suggests the role of ortho-phenolic substitution in enhancing activity and selectivity. Compound 12 emerges as a promising lead, warranting further optimization and biological evaluation in future studies.<\/jats:p>","DOI":"10.3390\/life16060979","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:57:17Z","timestamp":1781161037000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["New Thieno[3,2-d]pyrimidin-4(3H)-one Schiff Bases as Selective Antileishmanial Agents"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3674-8120","authenticated-orcid":false,"given":"Neriman","family":"Mor","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Kafkas University, 36100 Kars, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-4656","authenticated-orcid":false,"given":"Bar\u0131\u015f","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Life Sciences and Technologies Application and Research Center, Kafkas University, 36000 Kars, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-3143","authenticated-orcid":false,"given":"Baycan","family":"Mor","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Sciences and Letters, Kafkas University, 36100 Kars, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5532-8802","authenticated-orcid":false,"given":"Feyzi Sinan","family":"Tokal\u0131","sequence":"additional","affiliation":[{"name":"Department of Material and Material Processing Technologies, Kars Vocational School, Kafkas University, 36100 Kars, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: A review","volume":"6","author":"Arenas","year":"2017","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1128\/CMR.14.2.229-243.2001","article-title":"Leishmaniasis: Current Status of Vaccine Development","volume":"14","author":"Handman","year":"2001","journal-title":"Clin. 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