Bioassay-guided screening and isolation of α-glucosidase and tyrosinase inhibitors from leaves of Morus alba

In this study, bioassay-guided fractionation of extracts from the leaves of Morus alba L led to the isolation of 15 bioactive constituents with alpha-glucosidase and tyrosinase inhibitory activities, among which prenylated stilbenes were proved to be a new group of alpha-glucosidase inhibitors apart from iminosugars derived from Morus alba. Their structures were identified on the basis of extensive spectroscopic analysis and chemical evidence, as well as comparing with data from the literature. Among them, compounds (2R)/(2S)-Euchrenone a(7) (6a/6b), Chalcomoracin (7), Moracin C(8), Moracin D (9) and Moracin N (10) exhibited a significant degree of alpha-glucosidase inhibitory activity with IC50 of 6.28, 2.59, 4.04, 2.54 and 2.76 mu M, respectively, while (2R)/(2S)-Euchrenone a(7) (6a/6b), Moracin N (10), Quercetin (13), Norartocarpetin (14), the interconvertible epimeric mixture of (2R)/(2S)-7-methoxyl-8-ethyl-2',4'-dihydroxylflavane-2-O-beta-D-glucopyranoside (1a/1b) and the interconvertible enantiomers of (2R)/(2S)-7-methoxyl-8-hydroxyethyl-2',4'-dihydroxylflavane (5a/5b) displayed a potent tyrosinase inhibitory effect with IC50 of 0.260, 0.924, 0.523, 0.0824, 0.616 and 0.528 mu M, respectively. Especially, (2R)-7-methoxyl-8-ethyl-2',4'dihydroxylflavane-2-O-beta-D-glucopyranoside (1a), (2S)-7-methoxyl-8-ethyl-2',4'-dihydroxylflavane-2-O-beta-D-glucopyranoside (1b), (2S)-8-hydroxyethy1-7,4'-dimethoxylflavane-2'-O-beta-D-glucopyranoside (2), (2R)-7-methoxyl-8-hydroxyethyl-2',4'-dihydroxylflavane (5a) and (2S)-7-methoxyl-8-hydroxyethyl-2',4'-dihydroxylflavane (5b) were identified as new compounds. (C) 2011 Elsevier Ltd. All rights reserved.