In vitro biological evaluation and molecular docking studies of natural and semisynthetic flavones from Gardenia oudiepe (Rubiaceae) as tyrosinase inhibitors

• Published in: Bioorganic chemistry 2019-02, Vol.82, p.241-245
• Main Authors: Santi, M.D., Bouzidi, C., Gorod, N.S., Puiatti, M., Michel, S., Grougnet, R., Ortega, M.G.
• Format: Article
• Language: English
• Subjects: Gardenia oudiepe; Molecular docking; Polymethoxylated flavones; Structure-activity relationships; Tyrosinase inhibitory activity
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.10.034

[Display omitted] •Polymethoxyflavones from Gardenia oudiepe were evaluated for tyrosinase inhibition.•Compounds with a 3′,4′-dimethoxy-5′-hydroxy B ring were the most active.•SAR conclusions were confirmed by molecular docking studies.•Flavone 1 may be a potential lead for the treatment of hyperpigmentary disorders. 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.