Differential growth inhibition of cultured mammalian cells: comparison of clinical antitumour agents and amsacrine derivatives.
The growth-inhibitory potencies in culture of a variety of clinical antitumour drugs have been compared using two widely studied cell lines: L1210 murine leukaemia and V79 Chinese hamster fibroblasts. Marked variations in the relative sensitivities of these two lines were observed with individual antimetabolites and DNA intercalating agents, while activities of alkylating agents and vinca alkaloids were similar for both cell lines. This experimental system was used to evaluate the possibility of designing intercalating drugs selective for a particular target cell. Results with derivatives of the antileukaemia agent amsacrine indicate that relative cytotoxicity can be modulated by simple monosubstitution within the 9-anilinoacridine ring system. The variation in ratios of inhibitory potencies within the latter series is similar to that observed for the structurally diverse group of clinically-utilized intercalators tested. These results suggest that amsacrine analogue development may provide agents having a different tumour spectrum and greater therapeutic utility than the parent drug.
D000477:Alkylating Agents / Q000494:pharmacology; D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D007364:Intercalating Agents / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice
D000477:Alkylating Agents; D000609:Aminoacridines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D000677:Amsacrine