In vitro biological evaluation and molecular docking studies of natural and semisynthetic flavones from Gardenia oudiepe (Rubiaceae) as tyrosinase inhibitors |
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Institution: | 1. Laboratoire de Pharmacognosie, UMR CNRS 8638 COMETE, Faculté de Pharmacie de Paris, Université Paris-Descartes, Sorbonne Paris Cité, 4, av. de l''Observatoire, 75006 Paris, France;2. Département de Pharmacie, Faculté de Médecine, Université de Tlemcen, 13000 Tlemcen, Algérie;3. Unité Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR 7245), Muséum National d''Histoire Naturelle, CNRS, Sorbonne Universités, CP52, 57 rue Cuvier, 75005 Paris, France;4. BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 5 rue J.-B. Clément, 92290 Châtenay-Malabry, France |
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Abstract: | Hyperpigmentation disorders are difficult to treat without causing permanent depigmentation or irritation. The most effective hypopigmenting agents are tyrosinase inhibitors, however some of those currently used have shown serious side effects. As several classes of flavonoids have already demonstrated ability to inhibit tyrosinase, a library of natural polymethoxyflavones isolated (1–7) from the bud exudate of Gardenia oudiepe and semi-synthetic derivatives (8,9) were evaluated. IC50 of the most active compounds were in the micromolar range. The strongest inhibitors 1, 2 and 3 all shared a 3′,4′-dimethoxy-5′-hydroxy trisubstituted B ring. These SAR conclusions were confirmed by molecular docking studies. The mode of interaction with the enzyme was elucidated, and important interactions between the most active compounds and catalytic residues of tyrosinase were observed. All of these data provided a library of compounds as potential leaders for the design of new depigmenting agents and formulations. |
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Keywords: | Polymethoxylated flavones Tyrosinase inhibitory activity Structure-activity relationships Molecular docking |
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