ISOLATION AND CYTOTOXIC EVALUATION OF MARINE SPONGE-DERIVED NORTERPENE PEROXIDES

The marine sponge Diacarnus cf. spinopoculum has provided a series of norterpenes, including five new compounds (7-11), two new ent-compound s [(-)-1a and (+)-1b], and three known compounds (2a, 2b, and 12). Eig ht of these compounds represent additional examples of the muqubilin/s igmosceptrellin classes (norsesterterpene peroxides) or the nuapapuin class (norditerpene peroxides). Also isolated were dinorditerpenones 1 1 and 12, which are biosynthetically related to the muqubilin/sigmosce ptrellin structure classes. In all, 11 compounds were evaluated for th eir cytotoxic properties using a soft agar assay system and the NCI's 60 cell-line screen. Compounds without peroxide functionality were ina ctive. Overall, the norsesterterpene peroxides were less selective as cytotoxins than norditerpene peroxide analogues. Two compounds, nuapap uin A methyl ester (3) and nuapapuin B (7), which were somewhat select ive in their cytotoxic behavior, were selected for further in vivo eva luation.