Synthesis and antitumor activity of structural analogues of the anticancer benzophenanthridine alkaloid fagaronine chloride.
The indenoisoquinoline analogue 4 of fagaronine chloride (2) has been prepared, as well as its positional isomer 20 and the corresponding mesylated derivatives 16 and 19. Compounds 4, 16, and 20 were tested against P388 lymphocytic leukemia and found to possess significant activity. A tricyclic analogue 24 was also synthesized and was devoid of cytotoxicity in the KB cancer cell culture system. The change in the substitution pattern of the A-ring on going from 4 to 20 was tolerated without producing a significant decrease in antitumor activity.
D000470:Alkaloids / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic