TOPOISOMERASE-II-MEDIATED DNA CLEAVAGE BY ADOCIAQUINOMES AND XESTOQUINOMES FROM THE PHILIPPINE SPONGE XESTOSPONGIA SP

Investigation of an orange Xestospongia sp. sponge collected at Cape B olinao in northern Luzon, Philippines, yielded the known compounds ado ciaquinones A and B (1, 2) and six new metabolites, secoadociaquinones A and B (3, 4), 14-methoxyxestoquinone (5), 15-methoxyxestoquinone (6 ), 15-chloro-14-hydroxyxestoquinone (7), and 14-chloro-15-hydroxyxesto quinone (8). All compounds showed inhibition of topoisomerase II in ca talytic DNA unwinding and/or decatenation assays. Furthermore, adociaq uinone B showed activity in a KSDS assay, suggesting it inhibits the e nzyme by freezing the enzyme-DNA cleavable complex. Interestingly, ado ciaquinone B did not displace ethidium bromide from DNA or unwind supe rcoiled DNA, implying it does not intercalate DNA.