{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:21:12Z","timestamp":1787822472474,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002543","name":"Pusan National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Retaining structural features that allow 2\u2010mercaptomethylbenzimidazole compounds to function as Cu(II) chelators,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010mercaptoethyl)benzamide (NMEB) derivatives\n                    <jats:bold>1a<\/jats:bold>\n                    \u2013\n                    <jats:bold>1m<\/jats:bold>\n                    were designed, synthesized, and assessed for their potential as Cu(II) chelators. Derivative\n                    <jats:bold>1m<\/jats:bold>\n                    inhibited mushroom tyrosinase (mTYR) activity twice as potently as kojic acid (KA) in the presence of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010DOPA. The mechanisms by which three derivatives, including\n                    <jats:bold>1m<\/jats:bold>\n                    , inhibit mTYR were elucidated through kinetic studies. Interestingly, all NMEB derivatives suppressed melanogenesis more potently than KA in B16F10 cells, significantly reducing melanin production in a concentration\u2010dependent manner. NMEB derivatives also inhibited cellular TYR activity in keeping\u00a0with their melanogenesis inhibition, indicating B16F10 cellular TYR inhibition to be the primary mechanism. Moreover, among these derivatives,\n                    <jats:bold>1a<\/jats:bold>\n                    inhibited zebrafish larval pigmentation hundreds of times more potently than KA. In mammalian cells and zebrafish larvae, NMEB derivatives showed even higher TYR\u2010inhibitory or antimelanogenesis potency than mushrooms. Due to differences in the amino acid sequence and location of TYRs, NMEB derivatives appear to differ in their inhibition of TYR activity and melanin production in different species. This study points out limitations in the development of novel TYR inhibitors based on mTYR inhibition results and provides fundamental data supporting their development as novel skin\u2010lightening agents.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70383","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:23:16Z","timestamp":1787552596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tyrosinase Inhibitors With Enhanced Potency in Mammalian and Vertebrate Models,\n                    <i>N<\/i>\n                    \u2010(2\u2010Mercaptoethyl)benzamide Derivatives: Design, Synthesis, and Evaluation"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5779-1333","authenticated-orcid":false,"given":"Hyunhee","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research 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