{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:43:34Z","timestamp":1787741014914,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of multi\u2010functional tyrosinase inhibitors derived from kojic acid (KA) and hydroquinone\u2010like diphenols were designed and synthesized using click chemistry. The in vitro enzymatic assay revealed that all compounds containing a free enolic structure showed excellent activity against tyrosinase (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.14\u20133.7\u2009\u00b5M), being significantly more potent than KA. The most active compounds were catechol (<jats:bold>6c<\/jats:bold>) and \u03b1\u2010naphthol (<jats:bold>6i<\/jats:bold>) analogs with 138\u2010 and 96\u2010fold higher potency than KA. On the other hand, all free phenolic compounds (<jats:bold>6a\u2010c<\/jats:bold> and <jats:bold>6g\u2010j<\/jats:bold>) derived from aromatic diols showed outstanding free radical scavenging activities superior to KA. Certainly, the \u03b1\u2010naphthol derivative <jats:bold>6i<\/jats:bold> with IC<jats:sub>50<\/jats:sub>\u2009=\u200910.1\u2009\u00b5M was the most active anti\u2010oxidant, being as potent as quercetin. The SAR analysis indicated that the enolic head of the conjugate molecules mainly contributes to the anti\u2010tyrosinase activity, and the free phenolic part of the molecules can offer anti\u2010oxidant potency. The anti\u2010melanogenic assay of the most promising derivative, <jats:bold>6i<\/jats:bold>, against melanoma (B16F10) cells demonstrated that the prototype compound <jats:bold>6i<\/jats:bold> can significantly reduce the melanin content, more effectively than KA. By using a conjugation strategy, we have improved the tyrosinase inhibitory and radical scavenging activity in the multi\u2010functional agents such as <jats:bold>6i<\/jats:bold> over the parent compound KA, being potentially useful in the treatment of hyperpigmentation and other skin disorders.<\/jats:p>","DOI":"10.1002\/ardp.202400380","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T18:14:49Z","timestamp":1730139289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Multi\u2010functional tyrosinase inhibitors derived from kojic acid and hydroquinone\u2010like diphenols for treatment of hyperpigmentation: Synthesis and in vitro biological evaluation"],"prefix":"10.1002","volume":"357","author":[{"given":"Morteza","family":"Ashooriha","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy Mazandaran University of Medical Sciences Sari Iran"},{"name":"Student Research Committee Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-2964","authenticated-orcid":false,"given":"Mehdi","family":"Khoshneviszadeh","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Kabiri","sequence":"additional","affiliation":[{"name":"Arnold &amp; Marie Schwartz College of Pharmacy and Health Sciences Long Island University New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Dehshahri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy Shiraz University of Medical Sciences Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahareh","family":"Hassani","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy Mazandaran University of Medical Sciences Sari Iran"},{"name":"Student Research Committee Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1665-6621","authenticated-orcid":false,"given":"Saeed","family":"Emami","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/app12063177"},{"key":"e_1_2_7_3_1","first-page":"13","volume":"7","author":"Desai S. 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