Sartorelli Patrícia, Andrade Samanta P, Melhem Márcia S C, Prado Frederico O, Tempone André G
Centro de Estudos Químicos, UNIFIEO, Centro Universitário FIEO, Av. Franz Voegeli, 300 Bloco Branco, 4 andar. CEP, Osasco, SP, Brasil.
Phytother Res. 2007 Jul;21(7):644-7. doi: 10.1002/ptr.2131.
Natural products represent a rich source of new chemical entities for the development of drugs for neglected diseases. Leishmaniasis still afflicts the poorest populations in the world, with 12 million cases worldwide. This work analysed crude extracts and fractions from the fruits of Cassia fistula against the most dramatic and fatal disease form of leishmaniasis, the visceral form (VL). Hexane extract from the fruits showed significant antileishmanial activity against the promastigote form of Leishmania L. chagasi. The bioguided fractionation resulted in the isolation of a sterol, clerosterol, which was further analysed in different models. Promastigotes presented an inhibitory concentration 50% (IC50) of 10.03 microg/mL and intracellular amastigotes demonstrated high susceptibility, with an IC50 of 18.10 microg/mL. Mammalian cytotoxicity was evaluated and it was demonstrated that clerosterol was 3.6-fold less toxic than the standard drug pentamidine. No antifungal activity of the isolated clerosterol was found. Future studies of the extracted compounds of Cassia fistula could be a useful tool for the development of new therapeutic agents for VL.
天然产物是开发用于治疗被忽视疾病药物的新化学实体的丰富来源。利什曼病仍然困扰着世界上最贫困的人群，全球有1200万病例。这项工作分析了决明子果实的粗提物和馏分对利什曼病最严重和致命的疾病形式——内脏型（VL）的作用。果实的己烷提取物对杜氏利什曼原虫前鞭毛体形式显示出显著的抗利什曼活性。生物导向分级分离导致分离出一种甾醇，clerosterol，并在不同模型中对其进行了进一步分析。前鞭毛体的半数抑制浓度（IC50）为10.03微克/毫升，细胞内无鞭毛体显示出高敏感性，IC50为18.10微克/毫升。评估了哺乳动物细胞毒性，结果表明clerosterol的毒性比标准药物喷他脒低3.6倍。未发现分离出的clerosterol有抗真菌活性。决明子提取化合物的未来研究可能是开发VL新治疗药物的有用工具。
