1. Topoisomerase II-mediated DNA cleavage by adocia- and xestoquinones from the Philippine sponge Xestospongia sp.
- Author
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Concepción GP, Foderaro TA, Eldredge GS, Lobkovsky E, Clardy J, Barrows LR, and Ireland CM
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents isolation & purification, Crystallography, X-Ray, DNA metabolism, Drug Screening Assays, Antitumor, Humans, Intercalating Agents, Magnetic Resonance Spectroscopy, Molecular Structure, Philippines, Quinones chemistry, Quinones isolation & purification, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, DNA drug effects, Porifera chemistry, Quinones pharmacology, Topoisomerase II Inhibitors
- 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.
- Published
- 1995
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