Journal
JOURNAL OF NATURAL PRODUCTS
Volume 69, Issue 3, Pages 373-376Publisher
AMER CHEMICAL SOC
DOI: 10.1021/np0504107
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Funding
- NCI NIH HHS [U19 CA050771-15, U19 CA050771, U19 CA050771-080003, U19 CA050771-130002, U19 CA050771-120002, U19 CA 50771, U19 CA050771-14] Funding Source: Medline
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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 mu g/mL, while the new compound stellettin J (3) induced 5% binding at 28 mu g/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.
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