Wide difference between the cytotoxicity of the 11-alpha-and 11-beta-cyano analogues of tilivalline and their epimeric conversion.
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.
Kohda
K
K
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Yamagami
N
N
Kasamatsu
T
T
Aoyama
T
T
Shioiri
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001570:Benzodiazepinones; C093067:tilivalline