Gnoatto Simone C B, Dassonville-Klimpt Alexandra, Da Nascimento Sophie, Galéra Philippe, Boumediene Karim, Gosmann Grace, Sonnet Pascal, Moslemi Safa
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre 90610-000, RS, Brazil.
Eur J Med Chem. 2008 Sep;43(9):1865-77. doi: 10.1016/j.ejmech.2007.11.021. Epub 2007 Dec 7.
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 microM as did apigenin (IC50=10 microM), whereas IC50 value of 4-OHA was 0.8 microM. 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.
对从巴拉圭冬青（一种在南美被用于制备名为马黛茶的植物）中提取的熊果酸及其衍生物抑制芳香化酶活性的效力进行了评估，并与植物雌激素芹菜素和甾体芳香化酶抑制剂4-羟基雄烯二酮（4-OHA）进行了比较。在所有测试的化合物中，只有熊果酸1显示出高效且剂量依赖性的芳香化酶抑制作用，其IC50值为32微摩尔，芹菜素也是如此（IC50 = 10微摩尔），而4-OHA的IC50值为0.8微摩尔。我们的结果表明，将茂金属部分引入熊果酸衍生物中会降低芳香化酶抑制作用。此外，对化合物结构/抑制效力关系的比较表明，A环的存在以及C3-OH和C17-COOH的构型似乎更有利于识别芳香化酶的活性位点并阻断其活性。
