Antitumoral activity of dipyrido [4,3-b] [3,4-f] indoles on L 1210 leukemia.
Newly synthesized dipyrido [4,3-b] [3,4-f] indole compounds have a structural similarity with the DNA intercalating agents ellipticines (pyrido-carbazoles). The procedure of synthesis of these compounds allows the addition of a lateral chain in position 1 of the nucleus. Comparison is made between different substitutions and the resulting cytotoxic and antitumoral effects. The most active compound of the serie (1-gamma-diethyl amino propyl amino)-5-methyl-dipyrido [4,3-b] [3,4-f] indole (called here BD40) protects mice against L1210 leukemia. At the non-toxic dose of 20 mg/kg, particularly, a single infection of this compound given one day after inoculation of 10(5) L1210 cells resulted in an increased life span of 69 per cent with one survivor at 60 days. A combination of cyclophosphamide and BD40 had a synergic effect on the life span of L1210 inoculated mice. The antitumoral action of these drugs may be linked to their intercalative action upon biding to DNA.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004611:Ellipticines / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007546:Isoquinolines; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004611:Ellipticines; D007211:Indoles; D007546:Isoquinolines; D011725:Pyridines; C024256:pazelliptine