Tiuman Tatiana Shioji, Ueda-Nakamura Tânia, Garcia Cortez Diógenes Aparício, Dias Filho Benedito Prado, Morgado-Díaz José Andrés, de Souza Wanderley, Nakamura Celso Vataru
Departamento de Análises Clínicas, Universidade Estadual de Maringá, Bloco I-90 Sala 123 CCS, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
Antimicrob Agents Chemother. 2005 Jan;49(1):176-82. doi: 10.1128/AAC.49.11.176-182.2005.
The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium. This isolated compound was identified through spectral analyses by UV, infrared, (1)H and (13)C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 microg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 microg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.
研究了小白菊内酯对亚马逊利什曼原虫的体外活性。小白菊内酯是一种从艾菊地上部分的水醇提取物中纯化得到的倍半萜内酯。该分离化合物通过紫外光谱、红外光谱、（1）H和（13）C核磁共振成像、DEPT（无畸变极化转移增强）、COSY（相关光谱）、HMQC（异核多量子相干）和电子喷雾电离质谱等光谱分析进行鉴定。小白菊内酯对亚马逊利什曼原虫的前鞭毛体形式显示出显著活性，在浓度为0.37微克/毫升时对细胞生长有50%的抑制作用。对于细胞内无鞭毛体形式，当以0.81微克/毫升使用时，小白菊内酯使巨噬细胞内寄生虫的存活指数降低了50%。该纯化化合物在培养中对J774G8巨噬细胞无细胞毒性作用，并且在使用抑制前鞭毛体形式的较高浓度时不会导致绵羊血液溶血。以明胶为底物的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示，用该分离化合物处理前鞭毛体后，半胱氨酸蛋白酶的酶活性增加。这一发现与小白菊内酯诱导的明显形态变化相关，如电子显微镜所见，出现类似于大溶酶体的结构以及鞭毛囊区域强烈的胞吐活性。这些结果为开发从天然产物中获得的具有杀利什曼原虫活性的新型药物提供了新的视角。
