Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
Exp Parasitol. 2012 Nov;132(3):383-7. doi: 10.1016/j.exppara.2012.08.019. Epub 2012 Sep 5.
Leishmaniasis and Chagas disease are parasitic protozoan infections that affect the poorest population in the world, causing high mortality and morbidity. As a result of highly toxic and long-duration treatments, novel, safe and more efficacious drugs are essential. In this work, the methanol (MeOH) extract from the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B) by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol B, with an in vitro EC(50) of 23 μg/mL against axenic promastigotes and an EC(50) of 22 μg/mL against intracellular amastigotes. Gibbilimbol B was also tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC(50) value of 17 μg/mL against trypomastigotes. To evaluate the cytotoxic parameters, this alkenylphenol was tested in vitro against NCTC cells, showing a CC(50) of 59 μg/mL and absent hemolytic activity at the highest concentration of 75 μg/mL. Using the fluorescent probe SYTOX Green suggested that the alkenylphenol disrupted the Leishmania plasma membrane upon initial incubation. Further drug design studies aiming at derivatives could be a promising tool for the development of new therapeutic agents for leishmaniasis and Chagas disease.
利什曼病和恰加斯病是寄生原生动物感染，影响世界上最贫穷的人口，导致高死亡率和发病率。由于毒性高和治疗时间长，新型、安全和更有效的药物是必不可少的。在这项工作中，从 Piper malacophyllum（胡椒科）叶的甲醇（MeOH）提取物中分离出一种烯基酚，通过光谱方法将其表征为 4-[(3'E)-癸烯基]苯酚（gibbilimbol B）。抗原生动物的体外试验首次表明，Leishmania (L.) infantum chagasi 对 gibbilimbol B 敏感，对无细胞前鞭毛体的体外 EC（50）为 23μg/mL，对细胞内无鞭毛体的 EC（50）为 22μg/mL。还测试了 gibbilimbol B 对抗锥虫活性（Trypanosoma cruzi）的作用，对锥虫体的 EC（50）值为 17μg/mL。为了评估细胞毒性参数，该烯基酚在体外对 NCTC 细胞进行了测试，显示 CC（50）为 59μg/mL，在最高浓度 75μg/mL 时没有溶血活性。使用荧光探针 SYTOX Green 表明，烯基酚在初始孵育时破坏了利什曼原虫的质膜。针对衍生物的进一步药物设计研究可能是开发利什曼病和恰加斯病新治疗药物的有前途的工具。
