Mendoza Daniel Torres, Ureña González Luis D, Ortega-Barría Eduardo, Capson Todd L, Rios Luis Cubilla
Laboratory of Natural Products, Faculty of Natural and Exact Sciences and Technology, Apartado 0824, University of Panama, Panama City, Republic of Panama.
J Nat Prod. 2003 Jul;66(7):928-32. doi: 10.1021/np030010o.
Five novel cassane diterpenes (1-5) with activity against Trypanosoma cruzi were isolated from leaves of Myrospermum frutescens. The structures were determined as 18-hydroxycassan-13,15-diene (1), 6beta,18-dihydroxycassan-13,15-diene (2), 6beta-hydroxy-18-acetoxycassan-13,15-diene (3), 18-acetoxy-13,15-diene-19-cassanoic acid (4), and 6beta,13beta-dihydroxy-18-acetoxycassan-14(17),15-diene (5). Structures were elucidated by spectroscopic analysis (NMR and HRCIMS) and by the synthesis of derivatives 2a and 2b. Compounds 3 and 5 were more active against the extracellular form of the parasite (11 and 16 microM, respectively) than the intracellular forms, while compounds 1 and 2 were more active against the more clinically relevant intracellular forms of the parasite (17 microM). Compounds 1 and 2 were approximately 9-fold more toxic toward T. cruzi than toward human fibroblasts, the cell type that serves as the parasite's mammalian host cell.
从弗鲁特状香脂树的叶子中分离出了五种对克氏锥虫具有活性的新型乌檀烷二萜（1-5）。其结构被确定为18-羟基乌檀-13,15-二烯（1）、6β,18-二羟基乌檀-13,15-二烯（2）、6β-羟基-18-乙酰氧基乌檀-13,15-二烯（3）、18-乙酰氧基-13,15-二烯-19-乌檀酸（4）以及6β,13β-二羟基-18-乙酰氧基乌檀-14(17),15-二烯（5）。通过光谱分析（核磁共振和高分辨电喷雾电离质谱）以及衍生物2a和2b的合成对结构进行了阐明。化合物3和5对寄生虫细胞外形式的活性更强（分别为11和16微摩尔），而化合物1和2对寄生虫临床上更相关的细胞内形式的活性更强（17微摩尔）。化合物1和2对克氏锥虫的毒性比对作为寄生虫哺乳动物宿主细胞的人成纤维细胞大约高9倍。
