Synthesis and biological activity of structural analogues of the anticancer benzophenanthridine alkaloid nitidine chloride.
The indenoisoquinoline analogue 9 of nitidine (1) has been prepared and found to possess significant anticancer activity against L1210 lymphoid leukemia, P388 lymphocytic leukemia, and B16 melanocarcinoma. Analogue 14, which lacks the B ring of nitidine (1), has also been synthesized. Compound 14 retains the in vitro toxicity associated with nitidine (1) but is devoid of antileukemic activity. The structural factors that may contribute to the difference in biological activity between the two closely related analogues 9 and 14 are discussed.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D053119:Benzophenanthridines; D002277:Carcinoma; D002460:Cell Line; D006801:Humans; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D009062:Mouth Neoplasms; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007202:Indicators and Reagents; D007546:Isoquinolines; D010617:Phenanthridines; C040991:2,3-dimethoxy-6-methyl-8,9-(methylenedioxy)-11H-indeno(1,2-c)isoquinoline; C040992:N-methyl-3-(3,4-(methylenedioxy)phenyl)-6,7-dimethoxyisoquinoline; C013615:nitidine