Abstract

In the present work, the MeOH extract from stem barks of Calophyllum brasiliense Cambess. (Clusiaceae) displayed activity against amastigote forms of Trypanosoma cruzi and Leishmania infantum and was subjected to a bioactivity-guided fractionation to give two related coumarins - calanolides E1 (1) and E2 (2). Compounds 1 and 2 were actives to T. cruzi with EC₅₀ values of 12.1 and 8.2 μM, respectively. When tested against L. infantum, the EC₅₀ values were 37.1 and 29.1 μM, respectively. Compound 2, corresponding to anti isomer, showed the best selectivity index (SI) with values >24.4 to T. cruzi and >6.9 to L. infantum in comparison to the syn isomer 1. Furthermore, using an in silico multi-parametric prediction, both compounds did not contain any PAINS sub-structures. Therefore, these data suggest that coumarins 1 and 2 may contribute as scaffolds for the design of novel drug candidates for leishmaniasis and Chagas disease.

摘要

在目前的工作中，来自Calophyllum brasiliense Cambess茎皮的甲醇提取物。(Clusiaceae) 对克氏锥虫和婴儿利什曼原虫的无鞭毛体形式表现出活性，并经过生物活性引导的分级分离得到两种相关的香豆素 - 胡豆内酯 E1 ( 1 ) 和 E2 ( 2 )。化合物1和2对T. cruzi具有活性，EC ₅₀值分别为 12.1 和 8.2 μM。当针对婴儿乳杆菌进行测试时， EC ₅₀值分别为 37.1 和 29.1 μM。化合物2，对应于反异构体显示出最佳选择性指数 (SI)，与顺式异构体1相比，对T. cruzi 的值 >24.4，对婴儿乳杆菌的值>6.9 。此外，使用计算机多参数预测，两种化合物都不包含任何 PAINS 子结构。因此，这些数据表明香豆素1和2可能有助于作为设计利什曼病和南美锥虫病的新型候选药物的支架。