title: Structure-cytotoxicity relationship of tilivalline derivatives.
abstract: Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and an indole substituent in its structure, and is cytotoxic toward mouse leukemia L1210 cells. In order to obtain more effective compounds, we have previously synthesized a variety of TV analogues. In this study, the cytotoxicity of these compounds has been evaluated. Among the compounds tested, the 11-beta-cyano compound, a TV analogue bearing the cyano group instead of the indole group, is approximately 100 times more cytotoxic than TV itself. The alpha-epimer of this cyano compound has about one-hundredth the cytotoxicity of the 11-beta-cyano compound. Structure-cytotoxicity relationships are discussed, including the effects of stereoisomers (alpha and beta) at the 11 position and substitution at the benzene moiety of TV.
authors.affiliation: Department of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shioiri
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: N
authors.initials: N
authors.lastname: Yamagami
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Kohda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001570:Benzodiazepinones; C093067:tilivalline