Reimão Juliana Quero, Migotto Alvaro Esteves, Kossuga Miriam H, Berlinck Roberto G S, Tempone André Gustavo
Laboratório de Toxinologia Aplicada, Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8 andar, Cerqueira Cesar, CEP 01246-000 São Paulo, São Paulo, Brazil.
Parasitol Res. 2008 Nov;103(6):1445-50. doi: 10.1007/s00436-008-1154-6. Epub 2008 Sep 2.
In the present investigation, we have evaluated the antileishmanial and antitrypanosomal activity of methanolic crude extracts obtained from eight species of cnidarians and of a modified steroid isolated from the octocoral Carijoa riisei. The antileishmanial activity of cnidarians crude extracts showed 50% inhibitory concentration (IC50) values in the concentration range between 2.8 and 93.3 microg/mL. Trypomastigotes of Trypanosoma cruzi were less susceptible to the crude extracts, with IC50 values in the concentration range between 40.9 and 117.9 microg/mL. The steroid (18-acetoxipregna-1,4,20-trien-3-one) displayed a strong antileishmanial activity, with an IC50 value of 5.5 microg/mL against promastigotes and 16.88 microg/mL against intracellular amastigotes. The steroid also displayed mammalian cytotoxicity (IC50 of 10.6 microg/mL), but no hemolytic activity was observed at the highest concentration of 12.5 microg/mL. The antileishmanial effect of the steroid in macrophages suggested other mechanism than macrophage activation, as no upregulation of nitric oxide was observed. The antitrypanosomal activity of the steroid resulted in an IC50 value of 50.5 microg/mL. These results indicate the potential of cnidarian natural compounds as antileishmanial drug candidates.
在本研究中,我们评估了从8种刺胞动物中获得的甲醇粗提物以及从八放珊瑚类的里氏卡里佐珊瑚(Carijoa riisei)中分离得到的一种修饰类固醇的抗利什曼原虫和抗锥虫活性。刺胞动物粗提物的抗利什曼原虫活性显示,其50%抑制浓度(IC50)值在2.8至93.3微克/毫升之间。克氏锥虫的无鞭毛体对粗提物的敏感性较低,IC50值在40.9至117.9微克/毫升之间。该类固醇(18 - 乙酰氧基孕甾 - 1,4,20 - 三烯 - 3 - 酮)表现出较强的抗利什曼原虫活性,对前鞭毛体的IC50值为5.5微克/毫升,对细胞内无鞭毛体的IC50值为16.88微克/毫升。该类固醇还表现出哺乳动物细胞毒性(IC50为10.6微克/毫升),但在最高浓度12.5微克/毫升时未观察到溶血活性。该类固醇在巨噬细胞中的抗利什曼原虫作用表明其作用机制并非巨噬细胞激活,因为未观察到一氧化氮的上调。该类固醇的抗锥虫活性导致IC50值为50.5微克/毫升。这些结果表明刺胞动物天然化合物作为抗利什曼原虫药物候选物的潜力。