Topoisomerase II-mediated DNA cleavage by adocia- and xestoquinones from the Philippine sponge Xestospongia sp.
Investigation of an orange Xestospongia sp. sponge collected at Cape Bolinao in northern Luzon, Philippines, yielded the known compounds adociaquinones 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-hydroxyxestoquinone (8). All compounds showed inhibition of topoisomerase II in catalytic DNA unwinding and/or decatenation assays. Furthermore, adociaquinone B showed activity in a KSDS assay, suggesting it inhibits the enzyme by freezing the enzyme-DNA cleavable complex. Interestingly, adociaquinone B did not displace ethidium bromide from DNA or unwind supercoiled DNA, implying it does not intercalate DNA.
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010679:Philippines; D011161:Porifera / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011809:Quinones; D059005:Topoisomerase II Inhibitors; D004247:DNA; C068501:xestoquinone