Tabernaelegantinals: Unprecedented cytotoxic bisindole alkaloids from Muntafara sessilifolia

Bioassay-guided fractionation of the stem bark of Muntafara sessilifolia has led to the isolation of six new vobasinyl-iboga bisindole alkaloids, tabernaelegantinals A, B and E, and (3'R)-hydroxytabernaelegantines A, C and D, together with six known monomeric indole and two bisindole alkaloids. The structures of these alkaloids were established by NMR and MS analysis. The bisindole alkaloids demonstrated cytotoxicity against the human lung MRC-5 and rat skeletal muscle L-6 cell lines whereas only one monomeric indole alkaloid was found to be cytotoxic. Tabernaemontanine acetate was found to be selectively antiplasmodial against the chloroquine-resistant strain FcB1 of Plasmodium falciparum (5.3 μM IC ₅₀) over mammalian cell lines (selectivity index > 45). The tabernaelegantinals share an unprecedented α-amino aldehyde moiety, the biosynthetic origin of which is discussed.