Topoisomerase II-Mediated DNA Cleavage by Adocia- and Xestoquinones from the Philippine Sponge Xestospongia sp.

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.

Cytotoxic isoquinoline quinones from sponges of the genusPetrosia

“…B [8][9][10]. The attachment of the amine end of taurine to the quinone ring was supported by an HMBC correlation observed between H-11 ( 4.08) and C-7 (149.6 ppm).…”

Chemical and bioactive diversities of marine sponge <i>Neopetrosia</i>

“…carbonaria, N. exigua, N. sapra, N. proxima, N. seriata and N. similis. Many quinone and hydroquinone derivatives have been obtained from Xestospongia specimen that identified to the genus level (Zhu et al, 1998;Concepción et al, 1995). Xestoquinone and halenaquinone have been found in marine sponge Adocia sp (Schmitz and Bloor, 1988).…”

Meroterpenes from Marine Invertebrates: Structures, Occurrence, and Ecological Implications

“…Both compounds showed cardiotonic properties and inhibitory activity against Ca 2+ ATPase, phosphatidylinositol 3-kinase, protein-tyrosine kinase, and mammalian topoisomerase I. In addition, halenaquinone ( 213 ) showed cytotoxic activity against KB and P388 cell lines and it inhibited recombinant human Cdc25B in vitro with IC 50 values of 0.7 μM [152,153]. From an Adocia sp.…”