Natural and semisynthetic flavonoids as tyrosinase inhibitors

MAI H.; ORTEGA MG; SANTI M., ; GROUGNET R.,; BOUZIDI C.

Otro; 4ª Reunión Internacional de Ciencias Farmacéuticas; 2016

Tyrosinase is an oxidase enzyme that catalyzes the biosynthesis of melanin, it is responsible for the pigmentation of skin, eyes and hair in mammals. Alterations in their synthesis lead to pathologies such as skin cancer, hyperpigmentation, melasma, nevus, etc. Moreover, the currently marketed products have numerous adverse effects. From Gardenia urvillei (Rubiaceae) specie endemic to New Caledonia, flavonoids were isolated and synthesized and have demonstrated anti-vascular and anti-parasitic activity. Antecedents inform flavonoids as inhibitors of mushroom tyrosinase (Tyr). Therefore, tyrosinase inhibitors of natural origin, which present minor adverse effects, are an alternative in the treatment of such diseases. The aim of this work was to evaluate the inhibitory activity of flavonoids isolated and semi-synthesized from Gardenia urvillei on Tyr.Exudate aerial parts of Gardenia urvillei were treated as expressed by Mai et al, obtaining: Santin (5,7-dihydroxy-3,4´, 6-trimethoxy) (F1), 5,7-dihydroxy-3, 3´, 4´, 5´, 6´-pentamethoxyflavone (F3), 3-methoxy-kaempferol (kaempferol-3-monomethyl) (F5) and 5,5´-dihydroxy-3, 7, 3´, 4´-tetramethoxyflavone (F17 ). F14 was obtained by methylation of 3-methoxy-kaempferol (F5) and F15 was obtained by acetylation of kaempferol. The inhibitory activity of flavonoids on Tyr was conducted according to the methodology described by Peralta et al. measuring the formation of dopachrome at 490 nm spectrophotometrically. The mean inhibitory concentrations (IC50) were estimated. F1 and F14 were inactive. F17 was the most active (17.660 ± 0.001μM), followed by F15 (49.5 ± 0.4μM), F3 (62.681 ± 0.001μM) and F5 (103.559 ± 0.001μM), comparing with the reference inhibitor, kojic acid (IC50 = 12.119 ± 0.001μM). It can be concluded that the flavonoid 5, 5´-dihydroxy-3,7,3´,4´-tetramethoxyflavone (F17) was the most active and the rest of the compounds showed moderate activity.At this moment these compounds are being evaluated on melanoma B16 tyrosinase mouse cells in order to obtain new candidates with potential applications in pharmaceutical and cosmetic industry.