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ID: ALA1128184
Journal: J Med Chem
Title: Topoisomerase II-mediated DNA cleavage by adocia- and xestoquinones from the Philippine sponge Xestospongia sp.
Authors: Concepción GP, Foderaro TA, Eldredge GS, Lobkovsky E, Clardy J, Barrows LR, Ireland CM.
Abstract: 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.
CiteXplore: 7473578
DOI: 10.1021/jm00022a016