Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition

The inhibitory potency of ursolic acid extracted from flex paraguariensis, a plant used in South American population for a tea preparation known as mate, and its derivatives to inhibit aromatase activity was assessed and compared to a phytoestrogen apigenin and a steroidal aromatase inhibitor 4-hyroxyandrostenedione (4-OHA). Among all compounds tested only ursolic acid 1 showed an efficient and dose-dependent aromatase inhibition with IC50 value of 32 mu M as did apigenin (IC50 = 10 mu M), whereas IC50 value of 4-OHA was 0.8 mu M. Our results show that the incorporation of a metallocene moiety into the ursolic acid derivatives decreases the aromatase inhibition. Moreover, comparison of the structure/inhibitory potency relationship of compounds indicates that the presence of cycle A and the configuration of C3-OH and C17-COOH seems to be more favourable to recognize the active site of aromatase and to block its activity. (C) 2007 Elsevier Masson SAS. All rights reserved.