Topoisomerase II-mediated DNA cleavage by adocia- and xestoquinones from the Philippine sponge Xestospongia sp

  • J Med Chem. 1995 Oct 27;38(22):4503-7. doi: 10.1021/jm00022a016.
G P Concepción  1 ,  T A Foderaro ,  G S Eldredge ,  E Lobkovsky ,  J Clardy ,  L R Barrows ,  C M Ireland
Affiliations
  • 1. Marine Science Institute, University of the Philippines, Quezón City, Philippines.
PMID: 7473578 DOI: 10.1021/jm00022a016
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.