Tyrosinase inhibitory lignans from the methanol extract of the roots of Vitex negundo Linn. and their structure-activity relationship

Phytochemical investigation of the methanol extract of Vitex negundo afforded eight lignans; negundin A1, negundin B 2, 6-hydroxy-4-(4-hydroxy-3-methoxy)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaledehyde 3, vitrofolal E 4, (+)-lyoniresinol 5, (+)-lyoniresinol-3 alpha-O-beta-D-glucoside 6, (+)-(-)-pinoresinol 7, and (+)-diasyringaresinol 8. The structures of these compounds were elucidated unambiguously by spectroscopic methods including ID and 2D NMR analysis and also by comparing experimental data with literature data. The tyrosinase inhibitory potency of these compounds has been evaluated and attempts to justify their structure-activity relationships have been made in the present work. The compound 5 was found to be the most potent (IC50 = 3.21 mu M) while other compounds demonstrated moderate to potent inhibitions. It was found that the substitution of functional group(s) at C-2 and C-3 positions and the presence of the -CH2OH group plays a vital role in the potency of the compounds. The compound 5 can act as a potential lead molecule to develop new drugs for the treatment of hyperpigmentation associated with the high production of melanocytes. (c) 2005 Elsevier GmbH. All rights reserved.