{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:13:05Z","timestamp":1786119185678,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A novel series of sulfur\u2010containing analogs derived from the 3\u2010hydroxy\u20106\u2010methyl\u20102\u2010((4\u2010phenylpiperazin\u20101\u2010yl)methyl)\u20104\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyran scaffold was synthesized. Spectroscopic techniques and elemental analysis confirmed their structures. The biological potential of these compounds, along with their previously reported bioisosteres, was assessed as tyrosinase inhibitors, as well as antitubercular and antidermatophytic agents. In all derivatives where the carbonyl group is converted to a thiocarbonyl group, tyrosinase inhibition increases significantly, with the most effective compounds being identified as compounds\n                    <jats:bold>6c<\/jats:bold>\n                    and\n                    <jats:bold>6d<\/jats:bold>\n                    , which carry the 4\u2010fluoro and 4\u2010nitro groups, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.143 and 0.121\u2009mg\/mL, respectively, compared with kojic acid (0.067\u2009mg\/mL). Molecular modeling predicted enhanced engagement with the copper ions in tyrosinase active site upon shifting from carbonyl to thiocarbonyl. Similarly, all thioxo\u2010based analogs (\n                    <jats:bold>6a\u2013d<\/jats:bold>\n                    ) demonstrated antimycobacterial activity comparable to that of the reference drug ethambutol, particularly against\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    . These compounds also showed pronounced antidermatophytic activity, with MIC values ranging from 1 to 2\u2009\u03bcg\/mL against\n                    <jats:italic>Trichophyton mentagrophytes<\/jats:italic>\n                    var.\n                    <jats:italic>erinacei, Epidermophyton floccosum<\/jats:italic>\n                    , and\n                    <jats:italic>Microsporum gypseum<\/jats:italic>\n                    . Cytotoxicity assays in HeLa and MRC\u20105 cell lines revealed that the compounds remained bioactive at non\u2010toxic concentrations (\u2009\u2265\u2009128\u2009\u03bcg\/mL). Overall, the replacement of the carbonyl group with a thioxo functionality markedly enhanced the bioactivity of the derivatives predictably through improved tyrosinase inhibition, highlighting their potential as promising lead scaffolds for the future development of multifunctional therapeutic agents.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70233","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T16:49:00Z","timestamp":1769532540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thioxo\u2010Based Kojic Acid Derivatives as Potent Tyrosinase Inhibitors With Antitubercular and Antidermatophytic Potential"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-7537","authenticated-orcid":false,"given":"G\u00fcl\u015fah","family":"Karakaya","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy \u0130zmir Katip \u00c7elebi University \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-4218","authenticated-orcid":false,"given":"Suat","family":"Sari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Hacettepe University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-9841","authenticated-orcid":false,"given":"Fatma Sezer Senol","family":"Deniz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy Faculty of Pharmacy Gazi University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-1186","authenticated-orcid":false,"given":"Berrin","family":"\u00d6z\u00e7elik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology Faculty of Pharmacy Gazi 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