{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:29:13Z","timestamp":1793579353706,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"5","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":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Toxoplasmosis, caused by the protozoan parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    , remains a serious global health concern, largely because current treatments with sulfonamides and pyrimethamine are toxic and increasingly ineffective due to rising drug resistance. In response, this study describes the design, synthesis, and laboratory evaluation of novel hybrid molecules that merge a quinoline backbone with either thiadiazole (compounds\n                    <jats:bold>8a<\/jats:bold>\n                    \u2013\n                    <jats:bold>e<\/jats:bold>\n                    ) or thiazole (compounds\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>d<\/jats:bold>\n                    ) bioactive groups to develop safer and more effective therapies. Cytotoxicity tests on mouse (L929) and human (Hs27) fibroblast cell lines revealed distinct safety profiles: the thiadiazole hybrids (\n                    <jats:bold>8a<\/jats:bold>\n                    \u2013\n                    <jats:bold>e<\/jats:bold>\n                    ) were significantly toxic to host cells, whereas the thiazole\u2010based versions (\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>d<\/jats:bold>\n                    ) were much safer, with several showing no toxicity even at 250\u2009\u00b5g\/mL. When tested against\n                    <jats:italic>T. gondii<\/jats:italic>\n                    , the quinoline\u2010thiazole hybrids proved the most effective. Notably,\n                    <jats:bold>12b<\/jats:bold>\n                    and\n                    <jats:bold>12c<\/jats:bold>\n                    achieved IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.40 and 0.52\u2009\u00b5g\/mL, respectively, better than the reference drug pyrimethamine (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.74\u2009\u00b5g\/mL). Compound\n                    <jats:bold>12c<\/jats:bold>\n                    emerged as the top candidate, with an excellent selectivity index (SI) of 71.0 in human Hs27 cells. Further mechanistic work showed that\n                    <jats:bold>12c<\/jats:bold>\n                    strongly inhibits tyrosinase, a potential parasitic target. Kinetic studies revealed a mixed\u2010type inhibition mechanism, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of approximately 5\u2009\u00b5M, 10 times more potent than kojic acid (48\u2009\u00b5M), a standard inhibitor. Molecular docking and dynamics simulations confirmed stable binding between\n                    <jats:bold>12c<\/jats:bold>\n                    and tyrosinase. Together, these findings underscore the therapeutic promise of the quinoline\u2010thiazole scaffold, particularly compound\n                    <jats:bold>12c<\/jats:bold>\n                    , as a lead for developing targeted, low\u2010toxicity anti\u2010toxoplasmosis drugs. The results are expected to expand the existing toolkit of small molecules targeting the parasite and reinforce the importance of molecular hybridization in drug development. Additional research is needed to clarify how these compounds work and to assess their effectiveness in living organisms in order to fully unlock their potential as anti\u2010parasitic drugs.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70334","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:24:36Z","timestamp":1781771076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Quinoline Tethered Thiadiazole\/Thiazole Derivatives as Potent Tyrosinase Inhibitors With Promising Anti\u2010\n                    <i>Toxoplasma gondii<\/i>\n                    Agents: Design, Synthesis, and Computational Analysis"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-0196","authenticated-orcid":false,"given":"Ahmed","family":"Sabt","sequence":"first","affiliation":[{"name":"Chemistry of Natural Compounds Department Pharmaceutical and Drug Industries Research Institute, National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Chyb","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-6952","authenticated-orcid":false,"given":"Aladdin M.","family":"Srour","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Bekier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Laboratory Medical Immunology Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa","family":"Farag","sequence":"additional","affiliation":[{"name":"Pesticide Chemistry Department Chemical Industries Research Institute, National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moataz A.","family":"Shaldam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Kafrelsheikh University Kafr El Sheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-8861","authenticated-orcid":false,"given":"Hoda Atef Abdelsattar","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pediatric Department Faculty of Medicine, Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-319X","authenticated-orcid":false,"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Gatkowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-1678","authenticated-orcid":false,"given":"Huda R. 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