Tyrosinase inhibitors from the fruits of Madhuca latifolia

Tyrosinase is a copper-containing enzyme that catalyzes melanin synthesis in skin melanocytes by oxidation. Eighteen compounds of different classes, i.e., pentacyclic triterpenes, flavonoids, steroids, aromatics, mono and triglycerides and straight chain hydrocarbons were isolated from the fruit pulp and seeds of Madhuca latifolia and were identified as betulinic acid 3-β-caprylate (1), stigmasterol (2), ursolic acid (3), p-hydroxyacetophenone (4), hydroquinone (5), 4-hydroxymethylbenzoate (6), quercetin (7), taxifolin (8), hexadecenoic acid (9), β-amyrin acetate (10), triglyceride of stearo-oleo-palmitin (11), erythrodiol 3-β-caprylate (12), oleanolic acid 3-β-caprylate (13), monoglyceride of oleic acid (14), nonacosane (15), madhushazone (16), madhusalmone (17), madhucic acid (18). Structural characterizations of these were made by comparison of ¹H and ¹³C NMR spectra with those reported in the literatures. The tyrosinase inhibitory potency of these compounds has been evaluated and attempts to justify their structure-acitivity relationships have been made in the present work. The compounds 3, 4, 5, 6a (acetyle derivative of 6), 7, 8a (acetyl derivative of 8), 16, 17, and 18 exhibited much better potency than the reference inhibitor kojic acid, whereas compound 3 was the most active among them.