{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:34:21Z","timestamp":1790624061711,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2025 Post-Doc. Development Program of Pusan National University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, we designed and synthesized 11 N-aryl-S-aryl-2-mercaptoacetamide derivatives as new tyrosinase inhibitors (TYRIs). Experiments with pyrocatechol violet confirmed that four derivatives showed copper-chelating abilities similar to or superior to those of well-known copper-chelating TYRIs like kojic acid (KA) and N-phenylthiourea. However, these four derivatives showed little or no inhibition of mushroom TYR (mTYR) activity and melanin production in B16F10 cells. Instead, derivatives with low copper chelation ability exhibited potent inhibitory effects on mTYR activity and melanin production in B16F10 cells. These findings suggest that the results of metal ion chelation by inhibitors in an enzyme-free environment do not always match those under metalloenzyme conditions because of the interactions between inhibitors and amino acid residues around the metalloenzyme active site. Owing to their favorable interactions with amino acids in the mTYR active site, two of the derivatives inhibited mTYR more effectively than KA. Probably for the same reason, three derivatives inhibited B16F10 cellular TYR more effectively than KA, and one derivative inhibited pigment production in zebrafish larvae much better than KA. This last derivative, which effectively exhibits TYR-inhibitory activity and suppresses melanin production in several species, is considered a promising compound for use as a TYRI in various fields.<\/jats:p>","DOI":"10.3390\/molecules31030422","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T15:48:30Z","timestamp":1769442510000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["N-Aryl-S-aryl-2-mercaptoacetamide Derivatives Effectively Inhibit Mushroom and Cellular Tyrosinase Activities, Melanin Production, and Pigmentation in Zebrafish Larvae: Regarding Copper Ion Chelation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-5572","authenticated-orcid":false,"given":"Hee Jin","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Seo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minchang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunhee","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonsoo","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6438-1780","authenticated-orcid":false,"given":"Yujin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3215-8828","authenticated-orcid":false,"given":"Hae Young","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-7112","authenticated-orcid":false,"given":"Hyung Ryong","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7528","DOI":"10.1039\/D3TB01132A","article-title":"Melanin: Insights into structure, analysis, and biological activities for future development","volume":"11","author":"Song","year":"2023","journal-title":"J. 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