DNA intercalating compounds as potential antitumor agents. 1. Preparation and properties of 7H-pyridocarbazoles.
The DNA intercalating compounds derived from 6H-pyridocarbazole (ellipticines, olivacines) elicit high antitumor properties. In order to get information about the mechanism of action of these agents it is necessary to study structurally related analogues. For this purpose, various derivatives of the four isomeric 7H-pyridocarbazoles were synthesized by a single photochemical process on indolylpyridylethylenes. These derivatives are able to intercalate into DNA. The DNA binding affinities vary in the range of 10(4) to 10(6) M-1, depending mainly on the nature of the substituent, nitrogen quaternization being the most enhancing factor. The position of the pyridinic nitrogen does not markedly affect the DNA binding affinity. Three quaternized compounds elicit a significative but low antileukemic activity on L1210 mice leukemia. The properties of 7H-pyridocarbazoles are discussed and compared to those of 6H-pyridocarbazoles (ellipticines and olivacines).
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000032:analysis; D007364:Intercalating Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D014783:Viscosity
D000970:Antineoplastic Agents; D002227:Carbazoles; D007364:Intercalating Agents; D004247:DNA