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

被引：109

作者：

Gnoatto, Simone C. B. ^{[1
,2
]}

Dassonville-Klimpt, Alexandra ^{[1
]}

Da Nascimento, Sophie ^{[1
]}

Galera, Philippe ^{[3
]}

Boumediene, Karim ^{[3
]}

Gosmann, Grace ^{[2
]}

Sonnet, Pascal ^{[1
]}

Moslemi, Safa ^{[3
]}

机构：

[1] Univ Picardie Jules Verne, EA DMAG 3901, Fac Med & Pharm, F-80037 Amiens 1, France

[2] Univ Fed Rio Grande do Sul, Fac Farm, BR-90610000 Porto Alegre, RS, Brazil

[3] Univ Caen, Lab Matrice Extracellulaire & Pathol, EA3214,, IFR ICORE 146,Fac Med,CHU Caen, F-14032 Caen, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 43卷 / 09期

关键词：

Aromatase; Ursolic acid; Breast cancer; Pentacyclic triterpene hemisynthesis; Ferrocene; Ilex paraguariensis; Mate;

D O I：

10.1016/j.ejmech.2007.11.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

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.

引用

页码：1865 / 1877

页数：13

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