{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:13:53Z","timestamp":1747185233341,"version":"3.40.5"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K04504"],"award-info":[{"award-number":["23K04504"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intern J of Cosmetic Sci"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tyrosinase inhibitors suppress melanogenesis in melanocytes. During a screening for tyrosinase inhibitors, however, we noticed some discrepancies in inhibitory efficacies between melanocytes and in\u00a0vitro assays. The compound (<jats:italic>S<\/jats:italic>)\u2010<jats:italic>N<\/jats:italic>\u2010{3\u2010[4\u2010(dimethylamino)phenyl]propyl}\u2010<jats:italic>N<\/jats:italic>\u2010methyl\u2010indan\u20101\u2010amine (GIF\u20102115) exerts antioxidative stress activity upon accumulation in late endosomes and lysosomes. GIF\u20102115 was also identified as a potent antimelanogenic reagent in B16F10 mouse melanoma cells. GIF\u20102115 inhibited the activity of mushroom tyrosinase and the lysates of B16F10 cells. However, structure\u2013activity relationship studies indicated that GIF\u20102238, which lacks the benzene ring in the aminoindan structure of GIF\u20102115, inhibited tyrosinase activity in\u00a0vitro but did not inhibit melanogenesis in B16F10 cells. The aim of the present study is to show the importance of the intracellular distribution of tyrosinase inhibitors in exerting their antimelanogenic activity in melanocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The intracellular distribution of compounds was monitored by linking with the fluorescent group of 7\u2010nitro\u20102,1,3\u2010benzoxadiazole (NBD). To mislocalize GIF\u20102115 to mitochondria, the mitochondria\u2010preferring fluoroprobe ATTO565 was used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reconfirmed the localization of GIF\u20102250 (GIF\u20102115\u2010NBD) not only to matured but also to early\u2010stage melanosomes. Although GIF\u20102286 (GIF\u20102238\u2010NBD) maintained tyrosinase inhibitory activity, it did not show specific intracellular localization. Moreover, when GIF\u20102115 was linked with ATTO565, the resultant compound GIF\u20102265 did not inhibit melanogenesis in B16F10 cells, despite its strong tyrosinase inhibitory activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that melanosomal localization is essential for the antimelanogenic activity of GIF\u20102115, and GIF\u20102115 derivatives may be new guides for drugs to endosomes and lysosomes as well as melanosomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ics.12949","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T06:14:02Z","timestamp":1707372842000},"page":"668-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melanosomal localization is required for <scp>GIF<\/scp>\u20102115\/2250 to inhibit melanogenesis in <scp>B16F10<\/scp> melanoma cells"],"prefix":"10.1111","volume":"46","author":[{"given":"Ayumi","family":"Sakurai","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoka","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyu","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Okajima","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saho","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Oh\u2010Hashi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"},{"name":"The United Graduate School of Drug Discovery and Medical Information Sciences of Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Science, Faculty of Engineering Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoji","family":"Furuta","sequence":"additional","affiliation":[{"name":"GIFU EXOSOME Co. 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