Potential Anticancer Agents XXXI. N-Demethylation of Fagaronine

Abstract

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.

In Vitro and In Vivo Activity of Benzo[c]phenanthridines against Leishmania amazonensis

“…l " Table 1 shows that only quaternary benzo[c]phenanthrines display significant activity on axenic amastigotes of L. amazonensis. This difference of activity between tertiary and quaternary benzo[c]phenanthridines was already observed on other biological models [16]. Furthermore, l " Table 1 shows that chelerythrine (5) is the most active compound, with an activity five times higher than the reference compound amphotericin B.…”

Pregnane Glycosides

“…The growth ratios were 20% and 53%, respectively. Duh et al [99] isolated stizophyllin and its ∆ 16 -hydrogenated derivative from the whole plant of Stizophyllum riparium and tested their cytotoxic activities against P-388 lymphocytic leukemia cultured cells [100]. Stizophyllin proved to be active, with an ED 50 value of 0.07 μg mL -1 .…”

Plant Anticancer Agents XXXVII. Constituents ofAmanoa oblongifolia

“…The isolates from A. oblongifolia were evaluated for cytotoxic potential as described previously (21,22 the P-388 test system (6). None of the other isolates obtained in this study exhibited activity against either cultured KB or P-388 cells.…”