Potential anticancer agents XXXI. N-demethylation of fagaronine.
Fusion of fagaronine (1) afforded N-demethyl fagaronine (2) and two minor desmethyl products. Through examination of spectral properties and derivatization, the structures were deduced to be 3, a tetramethoxy derivative, and 5, a derivative bearing a hydroxy (rather than a methoxy) group at position-8. Acetylation of 2 afforded a monoacetate derivative (4), and similarly, a diacetate (6) was produced from 5. Compounds 2-6 were substantially less cytotoxic than 1, as judged by KB or P-388 cell culture assays, supporting the functional importance of the quaternary nitrogen atom. The results obtained to date for fagaronine in tumor panel-testing are also presented, and the marginal cytotoxic activity demonstrated by compounds 5 and 6 against cultured P-388 cells is discussed in terms of mechanisms of action of the parent compound.
D000470:Alkaloids; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D053119:Benzophenanthridines; D055598:Chemical Phenomena; D002621:Chemistry; D003640:Dealkylation; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010617:Phenanthridines
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D010617:Phenanthridines; C002066:fagaronine