Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase β to DNA

Jason A. Clement, Mei Li, Sidney Hecht, David G I Kingston

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 β. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and 23% binding, respectively, at 28 μg/mL, while the new compound stellettin J (3) induced 5% binding at 28 μg/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 β binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase β covalent binary complex.

Original languageEnglish (US)
Pages (from-to)373-376
Number of pages4
JournalJournal of Natural Products
Volume69
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

DNA-directed DNA polymerase
DNA-Directed DNA Polymerase
triterpenoids
Assays
DNA
Stabilization
ovarian neoplasms
Porifera
assays
Cytotoxicity
Biological Products
Ovarian Neoplasms
cytotoxicity
Cells
cell lines
Cell Line
extracts
methodology

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase β to DNA. / Clement, Jason A.; Li, Mei; Hecht, Sidney; Kingston, David G I.

In: Journal of Natural Products, Vol. 69, No. 3, 03.2006, p. 373-376.

Research output: Contribution to journalArticle

@article{75564f63754447e6b4c5b165c47dd5d7,
title = "Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase β to DNA",
abstract = "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 β. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29{\%} and 23{\%} binding, respectively, at 28 μg/mL, while the new compound stellettin J (3) induced 5{\%} binding at 28 μg/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 β binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase β covalent binary complex.",
author = "Clement, {Jason A.} and Mei Li and Sidney Hecht and Kingston, {David G I}",
year = "2006",
month = "3",
doi = "10.1021/np0504107",
language = "English (US)",
volume = "69",
pages = "373--376",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase β to DNA

AU - Clement, Jason A.

AU - Li, Mei

AU - Hecht, Sidney

AU - Kingston, David G I

PY - 2006/3

Y1 - 2006/3

N2 - 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 β. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and 23% binding, respectively, at 28 μg/mL, while the new compound stellettin J (3) induced 5% binding at 28 μg/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 β binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase β covalent binary complex.

AB - 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 β. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and 23% binding, respectively, at 28 μg/mL, while the new compound stellettin J (3) induced 5% binding at 28 μg/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 β binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase β covalent binary complex.

UR - http://www.scopus.com/inward/record.url?scp=33645996023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645996023&partnerID=8YFLogxK

U2 - 10.1021/np0504107

DO - 10.1021/np0504107

M3 - Article

VL - 69

SP - 373

EP - 376

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 3

ER -