Cunha Wilson Roberto, Crevelin Eduardo J, Arantes Glenda M, Crotti Antonio E Miller, Andrade e Silva Márcio L, Furtado Niege A J Cardoso, Albuquerque Sérgio, Ferreira Daniele Da Silva
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas da Universidade de Franca, Franca, SP, Brasil.
Phytother Res. 2006 Jun;20(6):474-8. doi: 10.1002/ptr.1881.
Triterpene acids, including ursolic acid (1), urjinolic acid (4) and oleanoic acid (5) along with a mixture of 2alpha-hydroxyursolic acid (2) and maslic acid (3) were isolated from methylene chloride extracts of the Miconia sellowiana and M. ligustroides species and their activities against the trypomastigote blood forms of Trypanosoma cruzi were evaluated. The potassium salt derivative of ursolic acid (1a) was also tested. The in vitro assays showed that compounds 1, 5 and 1a were the most active (IC(50) 17.1 microm, 12.8 microm and 8.9 microm, respectively). In contrast, a mixture of 2 plus 3, that exhibit a hydroxyl at C-2 and C-3, is much less potent than a mixture of 1 and 5 (IC(50) 48.5 microm and 11.8 microm, respectively). In the same manner, compound 4, that differs from 5 by two additional hydroxyl groups (at C-2 and C-23) displayed weak trypanocidal activity (IC(50) 76.3 microm) when compared with the other triterpenes. These results suggest that the free hydroxyl at C-3 and the polarity of C-28 are the most influential structural features for determining the in vitro trypanocidal activity of triterpenes. In vivo assays were also undertaken for the most active compounds 1, 1a and the mixture of 1 plus 5. The most significant reduction in parasite number in the parasitemic peak were obtained for compound 1 and its salt derivative 1a (75.7% and 70.4%, respectively). Moreover, the survival time was increased for all the treated animals.
从黄脉番荔枝和女贞叶番荔枝的二氯甲烷提取物中分离出了三萜酸，包括熊果酸（1）、乌金诺酸（4）和齐墩果酸（5），以及2α - 羟基熊果酸（2）和马斯里酸（3）的混合物，并评估了它们对克氏锥虫无鞭毛体血期的活性。还测试了熊果酸（1）的钾盐衍生物（1a）。体外试验表明，化合物1、5和1a活性最强（IC50分别为17.1微摩尔、12.8微摩尔和8.9微摩尔）。相比之下，在C - 2和C - 3位有羟基的2加3的混合物，其效力远低于1和5的混合物（IC50分别为48.5微摩尔和11.8微摩尔）。同样，与其他三萜相比，与5相差两个额外羟基（在C - 2和C - 23位）的化合物4显示出较弱的杀锥虫活性（IC50为76.3微摩尔）。这些结果表明，C - 3位的游离羟基和C - 28的极性是决定三萜体外杀锥虫活性的最具影响力的结构特征。还对活性最强的化合物1、1a以及1加5的混合物进行了体内试验。在血虫高峰期，化合物1及其盐衍生物1a使寄生虫数量减少最为显著（分别为75.7%和70.4%）。此外，所有治疗动物的存活时间都延长了。
