Evaluation of new sesquiterpene quinones from two Dysidea sponge species as inhibitors of protein tyrosine kinase

The Journal of Organic Chemistry
1992.0

Abstract

Our program to discover inhibitors of enzymes thought to be important in tumorigenesis motivated a study of marine 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 ≤28 μM and was considered to be moderately active against this enzyme. The other compounds were inactive.

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