Plant antitumor agents, 27. Isolation, structure, and structure activity relationships of alkaloids from Fagara macrophylla.
The known alkaloids nitidine chloride [1] and 6-oxynitidine [2] and a new compound 6-methoxy-5,6-dihydronitidine [3] have been isolated from Fagara macrophylla. Compound 3 was the major product and was shown to be an artifact. The alkaloids 1 and 3 have been interconverted by treatment of 1 under basic conditions or 3 under acidic conditions. On sublimation 1 and 3 formed 8,9-dimethoxy-2,3-methylenedioxybenzo[c]phenanthridine [4] which could then be converted to 5,6-dihydronitidine [5]. The alkaloids 1 and 3 are about equipotent in P-388 mouse leukemia, giving high T/C values of 240-260% at doses of 30-50 mg/kg. The other compounds were inactive. The structural requirement for antitumor activity in the phenanthridine series is the ability to form a C-6 iminium ion.
Research Triangle Institute, North Carolina 27709.
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D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification*; D002470:Cell Survival / Q000187:drug effects; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010946:Plants, Medicinal / Q000032:analysis*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic