1,2,3-Triazole-based kojic acid analogs as potent tyrosinase inhibitors: Design,synthesis and biological evaluation |
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| Institution: | 1. Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari, Italy;2. Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, Vancouver, BC, Canada;3. Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal;4. Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal;5. Dipartimento Politecnico, Laboratori di Tecnologie Chimiche, Università di Udine, Via del Cotonificio 108, 33100 Udine, Italy;6. Dipartimento di Chimica e Farmacia, Università di Sassari, Sassari, Italy |
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| Abstract: | A series of kojic acid-derived compounds 6a-p bearing aryloxymethyl-1H-1,2,3-triazol-1-yl moiety were designed by modifying primary alcoholic group of kojic acid as tyrosinase inhibitors. The target compounds 6a-p were synthesized via click reaction. All compounds showed very potent anti-tyrosinase activity (IC50s = 0.06–6.80 µM), being superior to reference drug, kojic acid. In particular, the naphthyloxy analogs 6o and 6p were found to be 31–155 times more potent than kojic acid. The metal-binding study of selected compound 6o revealed that the prototype compound possesses metal-chelating ability, particularly with Cu2+ ions. The promising compounds 6o and 6p had acceptable safety profile as demonstrated by cytotoxicity assay against melanoma (B16) cell line and Human Foreskin Fibroblast (HFF) cells. |
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| Keywords: | Click reaction Hyperpigmentation Kojic acid 1 2 3-Triazole Tyrosinase inhibitor |
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