Petri e Silva Simone Carolina Soares, Palace-Berl Fanny, Tavares Leoberto Costa, Soares Sandra Regina Castro, Lindoso José Angelo Lauletta
Laboratório de Soroepidemiologia e Imunobiologia, do Instituto de Medicina Tropical da, Universidade de São Paulo, Brazil.
Laboratório de Planejamento de Desenvolvimento de Fármacos, Faculdade de Ciências Farmacêuticas da, Universidade de São Paulo, Brazil.
Exp Parasitol. 2016 Apr;163:68-75. doi: 10.1016/j.exppara.2016.01.007. Epub 2016 Jan 18.
Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies.
利什曼病是一种被忽视的热带疾病，在多个国家影响着约100万人。临床表现取决于利什曼原虫与宿主免疫反应之间的相互作用。目前针对利什曼病的治疗选择有限，且会引发严重的副作用。在本研究中，我们测试了硝基杂环化合物（BSF系列）作为对抗利什曼原虫的新替代物。使用MTT比色法在婴儿利什曼原虫（利什曼原虫属）前鞭毛体和细胞内无鞭毛体中测量其活性。此外，我们通过流式细胞术评估前鞭毛体的磷脂酰丝氨酸暴露情况，并通过格里斯方法测量一氧化氮的产生。硝基杂环化合物（BSF系列）对婴儿利什曼原虫（利什曼原虫属）前鞭毛体显示出活性，促使前鞭毛体暴露磷脂酰丝氨酸，减少细胞内无鞭毛体数量并增加一氧化氮的产生。选择性指数对利什曼原虫比对巨噬细胞更为显著。与两性霉素B相比，我们的化合物呈现出更高的半数抑制浓度（IC50），然而选择性指数对寄生虫比对两性霉素B更具特异性。总之，在体外研究中，这些硝基杂环化合物显示出作为抗利什曼病药物的潜力。
