{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:48:26Z","timestamp":1788320906916,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["RGP1\/212\/46"],"award-info":[{"award-number":["RGP1\/212\/46"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    As a neglected tropical disease, Leishmaniasis continues to pose a serious threat to world health, especially in areas with limited resources. There is a pressing need for safer and more effective antileishmanial drugs due to the limited efficacy, toxicity, and rising resistance of available agents. We report the rational design, synthesis, and biological evaluation of a novel series of 15 hybrid compounds (\n                    <jats:bold>3a\u2010o<\/jats:bold>\n                    ), utilizing the thiazole and semicarbazone pharmacophores, two privileged scaffolds recognized for their wide range of biological activity. Both intracellular amastigote and promastigote forms of\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    were used to test the synthesized compounds' antileishmanial potential. With IC\u2085\u2080 values ranging from 2.97 to 10.18\u2009\u00b5M against promastigotes and from 3.47 to 12.36\u2009\u00b5M against amastigotes, a number of compounds demonstrated greater activity than the reference medication miltefosine. Selectivity indices revealed that compounds\n                    <jats:bold>3c<\/jats:bold>\n                    ,\n                    <jats:bold>3d<\/jats:bold>\n                    ,\n                    <jats:bold>3h<\/jats:bold>\n                    , and\n                    <jats:bold>3i<\/jats:bold>\n                    were the most potent, exhibiting a desirable balance between efficacy and cytotoxicity. The robust binding affinities and consistent interactions of these lead compounds inside the PTR1 and DHFR active sites were further supported by in silico docking. In conclusion, this study presents a novel chemotype that shows great promise for future advancement as a potent and focused antileishmanial treatment.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70275","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T07:45:59Z","timestamp":1774856759000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Thiazole\u2010Semicarbazone Hybrids as Dual\u2010Stage Inhibitors of\n                    <i>Leishmania major<\/i>\n                    Growth: Design, Synthesis, and Mechanistic Insights"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-4364","authenticated-orcid":false,"given":"Moataz A.","family":"Shaldam","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh 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