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

The inhibitory potency of ursolic acid extracted from Ilex paraguariensis, a plant used in South American population for a tea preparation known as maté, 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 μM as did apigenin (IC50 = 10 μM), whereas IC50 value of 4-OHA was 0.8 μM. 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.

Graphical abstractEvaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition: The inhibitory potency of ursolic acid and its derivatives to inhibit aromatase activity was assessed. Only ursolic acid 1 showed an efficient and dose-dependent aromatase inhibition. Figure optionsDownload full-size imageDownload as PowerPoint slide