8-Isocyanoamphilecta-11(20), 15-diene, a new antimalarial isonitrile diterpene from the sponge Ciocalapata sp.

A new isonitrile diterpene of the amphilectane family, 8-isocyanoamphilecta-11(20), 15-diene (4), was isolated from the sponge Ciocalapata sp., along with three known isonitriles, 8,15-diisocyano-11(20)-amphilectene (1), 7-isocyanoamphilecta-11(20), 15-diene (2), and 8-isocyanoamphilecta-11(20), 14-diene (3), and two steroidal peroxides, ergosterol peroxide (5) and 5 alpha,9 alpha-epidioxy-8 alpha,14 alpha-epoxy-(22E)-ergosta-6,22-dien-3 beta-ol (6). The structure of the new isonitrile was elucidated spectroscopically. In addition, anomalous multiplicities in the NMR spectra of some isolated isonitriles were observed and are reported here. The four isonitriles were strongly active against Plasmodium falciparum K1 with IC(50) in a range of 0.09-1.07 mmol/L. Except for 1, which was cytotoxic against both MCF-7 and fibroblast cell lines, the other three diterpenes showed no significant cytotoxicity against either targeted cell lines. On the other hand, the steroidal peroxides 5 and 6, which were less active in the antimalarial bioassay (IC(50) values of 6.28 and 7.13 mmol/L, respectively), were strongly cytotoxic against MCF-7 (IC(50) values of 0.025 and 0.003 mu mol/L, respectively), with very little toxicity against human fibroblasts.