title: Wide difference between the cytotoxicity of the 11-alpha-and 11-beta-cyano analogues of tilivalline and their epimeric conversion.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kohda
authors.forename: N
authors.initials: N
authors.lastname: Yamagami
authors.forename: T
authors.initials: T
authors.lastname: Kasamatsu
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: T
authors.initials: T
authors.lastname: Shioiri
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001570:Benzodiazepinones; C093067:tilivalline