FROM INACTIVE NORTOPSENTIN-D, A NOVEL BIS(INDOLE) ALKALOID ISOLATED FROM THE AXINELLID SPONGE DRAGMACIDON SP FROM DEEP WATERS SOUTH OF NEW-CALEDONIA, TO A STRONGLY CYTOTOXIC DERIVATIVE

Nortopsentin D (5), a bis(indole) alkaloid unique for bearing a 2-amin o-methylimidazole appendage at the central 1H-imidazol-5(4H)-one nucle us, was isolated in abundance, besides the putative biogenetic precurs or 6 of its appendage, from the deep-water axinellid sponge Dragmacido n sp. Structural elucidation of 5 by NMR and MS methods heavily relied on its N-methyl derivatives 8-11. Unusually for topsentin-type struct ures, natural 5 and semisynthetic methyl derivatives 8 and 10 proved i nactive on KB tumoural cells, while introduction of the last three met hyl groups, amazingly led to highly cytotoxic 11.