EVALUATION OF NEW SESQUITERPENE QUINONES FROM 2 DYSIDEA SPONGE SPECIES AS INHIBITORS OF PROTEIN TYROSINE KINASE

Our program to discover inhibitors of enzymes thought to be important in tumorigenesis motivated a study of marme sponge-derived sesquiterpene quinones (hydroquinones) against pp60v-src protein tyrosine kinase (PTK). Five new metabolites were isolated from the sponge Dysidea avara including melemeleone A (3), melemeleone B (4),18-methoxyavarone (6a), popolohuanone-C (8), and popolohuanone-D (9). These were accompanied by two known compounds, (+)-avarol (2a) and (+)-19-methoxyavarone (7). All of these compounds possess a 4,9-friedodrimane array linked to a quinone moiety containing additional heteroatoms. The new structures were determined from analysis of spectroscopic data, and all compounds were tested for inhibitory activity against pp60v-src PTK. Compound 4 had an IC50 of almost-equal-to 28 muM and was considered to be moderately active against this enzyme. The other compounds were all inactive.