Morais Thiago R, da Costa-Silva Thais A, Tempone Andre G, Borborema Samanta Etel T, Scotti Marcus T, de Sousa Raquel Maria F, Araujo Ana Carolina C, de Oliveira Alberto, de Morais Sérgio Antônio L, Sartorelli Patricia, Lago João Henrique G
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972270, Brazil.
Centro de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP 01246902, Brazil.
Molecules. 2014 May 5;19(5):5761-76. doi: 10.3390/molecules19055761.
Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.
利什曼病和恰加斯病是由寄生原生动物引起的疾病，影响着世界上最贫困的人群，导致高死亡率和高发病率。由于现有治疗方法毒性高且疗程长，因此发现新型、安全且更有效的药物至关重要。在这项研究中，研究了从巴西胡椒（漆树科）叶片中分离出的三种天然羽扇豆烷三萜类化合物及其九种半合成衍生物对婴儿利什曼原虫和克氏锥虫的体外抗寄生虫活性和对哺乳动物的细胞毒性。克氏锥虫的锥鞭毛体是最敏感的寄生虫，七种化合物表现出杀锥虫活性，IC50值在15至58μg/mL之间。四种化合物对利什曼原虫的细胞内无鞭毛体具有选择性，IC50值在28至97μg/mL之间。通过对核磁共振（NMR）数据以及电喷雾电离质谱（ESI-MS）的全面分析，完成了三萜类化合物的完整表征。此外，还使用决策树进行了构效关系研究。
