Passos Carlos Luan Alves, Ferreira Christian, Soares Deivid Costa, Saraiva Elvira Maria
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
PLoS One. 2015 Oct 30;10(10):e0141778. doi: 10.1371/journal.pone.0141778. eCollection 2015.
Stilbene-based compounds show antitumoral, antioxidant, antihistaminic, anti-inflammatory and antimicrobial activities. Here, we evaluated the effect of the trans-resveratrol analogs, pterostilbene, piceatannol, polydatin and oxyresveratrol, against Leishmania amazonensis.
METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrated a low murine macrophage cytotoxicity of all four analogs. Moreover, pterostilbene, piceatannol, polydatin and oxyresveratrol showed an anti-L. amazonensis activity with IC50 values of 18 μM, 65 μM, 95 μM and 65 μM for promastigotes, respectively. For intracellular amastigotes, the IC50 values of the analogs were 33.2 μM, 45 μM, 29 μM and 30.5 μM, respectively. Among the analogs assayed only piceatannol altered the cell cycle of the parasite, increasing 5-fold the cells in the Sub-G0 phase and decreasing 1.7-fold the cells in the G0-G1 phase. Piceatannol also changed the parasite mitochondrial membrane potential (ΔΨm) and increased the number of annexin-V positive promastigotes, which suggests incidental death.
CONCLUSION/SIGNIFICANCE: Among the analogs tested, piceatannol, which is a metabolite of resveratrol, was the more promising candidate for future studies regarding treatment of leishmaniasis.
基于芪的化合物具有抗肿瘤、抗氧化、抗组胺、抗炎和抗菌活性。在此，我们评估了反式白藜芦醇类似物紫檀芪、白皮杉醇、虎杖苷和氧化白藜芦醇对亚马逊利什曼原虫的作用。
方法/主要发现：我们的结果表明，所有四种类似物对小鼠巨噬细胞的细胞毒性较低。此外，紫檀芪、白皮杉醇、虎杖苷和氧化白藜芦醇对亚马逊利什曼原虫均显示出抗活性，前鞭毛体的IC50值分别为18 μM、65 μM、95 μM和65 μM。对于细胞内无鞭毛体，类似物的IC50值分别为33.2 μM、45 μM、29 μM和30.5 μM。在所检测的类似物中，只有白皮杉醇改变了寄生虫的细胞周期，使亚G0期的细胞增加了5倍，G0-G1期的细胞减少了1.7倍。白皮杉醇还改变了寄生虫的线粒体膜电位（ΔΨm），并增加了膜联蛋白-V阳性前鞭毛体的数量，这表明存在意外死亡。
结论/意义：在所测试的类似物中，作为白藜芦醇代谢产物的白皮杉醇是未来治疗利什曼病研究中最有前景的候选物。
