Synthesis and biological properties of some 6H-pyrido[4,3-b]carbazoles.
The effect of methyl substitution on the biological properties of the ellipticines was reexamined. 9-Hydroxy-6H-pyrido[4,3-b]carbazole was synthesized and shown to be devoid of antitumor activity in murine P388 lymphocytic leukemia in mice. 5-(Hydroxymethyl)-11-methyl-6H-pyrido[4,3-b]carbazole (46) and its N-methylcarbamate (48) were synthesized and their effect on macromolecular synthesis in HeLa cells and their antitumor properties were compared with those of ellipticine. In contrast to the alkaloid 1 and the hydroxymethyl derivative 46, which produced partially reversible inhibition of [3H]thymidine incorporation, the carbamate ester irreversibly blocked incorporation of the tritiated pyrimidine. The ester was also a more potent antitumor agent in P388 lymphocytic leukemia than 1 or 46.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D004611:Ellipticines / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D002227:Carbazoles; D004611:Ellipticines; C053112:5-(hydroxymethyl)-11-methyl-6H-pyrido(4,3-b)carbazole N-methylcarbamate; C034192:ellipticine; D013936:Thymidine; D014529:Uridine