Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase beta to DNA.
Four isomalabaricane triterpenoids were isolated from an extract of the sponge Rhabdastrella globostellata that was active in an assay measuring stabilization of the binding of DNA with DNA polymerase beta. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and 23% binding, respectively, at 28 microg/mL, while the new compound stellettin J (3) induced 5% binding at 28 microg/mL. The new compound stellettin K (4) had no activity in the binding assay. The compounds were characterized by spectroscopic methods. These compounds displayed varying levels of activity toward the A2780 ovarian cancer cell line, revealing structure-based effects on both the level of cytotoxicity and DNA-polymerase beta binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase beta covalent binary complex.
Clement
Jason A
JA
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, 24061, USA.
Li
Mei
M
Hecht
Sidney M
SM
Kingston
David G I
DG
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005367:Fiji; D006801:Humans; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014315:Triterpenes; D004247:DNA; D019951:DNA Polymerase beta