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Novel Kojic Acid-Thiadiazole-Urea Hybrids: Potent Tyrosinase Inhibitors With Enhanced Anti-Melanogenic Activity Publisher Pubmed



Mojaddami A ; Hamzi M ; Khoshneviszadeh M ; Kabiri M ; Attarroshan M ; Foroumadi A ; Toolabi M
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Source: Archiv der Pharmazie Published:2025


Abstract

A new class of kojic acid–derived tyrosinase inhibitors was rationally designed through the incorporation of a thiadiazole-urea framework. Accordingly, a series of 1-(aryl)-3-(5-{[(5-hydroxy-4-oxo-4H-pyran-2-yl)methyl]thio}-1,3,4-thiadiazol-2-yl)urea derivatives was synthesized starting from thiosemicarbazide. Through this approach, 13 new compounds were prepared with good yields via a straightforward procedure. The strategy involved substituting the hydroxymethyl group with a thiadiazol-urea pharmacophore, leading to the discovery of compounds that exhibited significantly enhanced inhibitory activity (IC50 range: 0.02–0.96 µM) compared to kojic acid (IC50 = 64.32 µM) against tyrosinase. Further kinetic, antioxidant, and docking studies, along with melanin content assays, were conducted to elucidate the mechanism of action for the most active compounds. © 2025 Deutsche Pharmazeutische Gesellschaft.
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