Kohda K, Yamagami N, Kasamatsu T, Aoyama T, Shioiri T
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Biochem Pharmacol. 1995 Apr 18;49(8):1063-8. doi: 10.1016/0006-2952(95)98502-z.
Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and is cytotoxic toward mammalian cells. The 11-beta-cyano TV analogue (1) is about one hundred times more cytotoxic to mouse leukemia L1210 cells than TV itself. In contrast, the 11-alpha-cyano TV analogue (2), an epimer of 1, has only about one-hundredth the cytotoxicity of 1. It was found that epimerization proceeded between 1 and 2 under physiological conditions, and the cytotoxicity of 2 is thought to be caused mainly by 1 that was formed from 2 during incubation in medium.
替利瓦林（TV）具有一个吡咯并[1,4]苯二氮䓬核，并且对哺乳动物细胞具有细胞毒性。11-β-氰基TV类似物（1）对小鼠白血病L1210细胞的细胞毒性比TV本身高约一百倍。相比之下，11-α-氰基TV类似物（2），即1的差向异构体，其细胞毒性仅为1的约百分之一。研究发现，在生理条件下1和2之间会发生差向异构化，并且认为2的细胞毒性主要是由在培养基中孵育期间由2形成的1所导致的。
