Synthesis and biological evaluation of analogues of butyrolactone I and molecular model of its interaction with CDK2

Organic & Biomolecular Chemistry
Miguel F BrañaM Teresa Domínguez

Abstract

A series of analogues of butyrolactone I, a natural product isolated from Aspergillus terreus that selectively inhibits the CDK2 and CDK1 kinases and that has been found to exhibit an interesting antiproliferative activity, have been synthesized. Its antitumor activity has been tested. Molecular models of the complex between butyrolactone I and the CDK2 active site have been built using a combination of conformational search and automated docking techniques. The stability of the resulting complexes has been assessed by molecular dynamics simulations and the experimental results obtained for the synthesized analogues are rationalized based on the molecular models.

References

Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Apr 27, 2000·Chemical & Pharmaceutical Bulletin·K V RaoG O Reddy
May 23, 2003·Angewandte Chemie·Axel HuweAthanassios Giannis
Jul 3, 2003·Nature Reviews. Drug Discovery·Simon J Teague
Jul 11, 2003·Journal of Medicinal Chemistry·Peter A SimsJ Andrew McCammon

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Citations

May 8, 2010·Organic Letters·Olga V Barykina, Barry B Snider
May 20, 2009·Organic Letters·Alan M Hyde, Stephen L Buchwald
Jun 21, 2006·Chemical Communications : Chem Comm·David TejedorFernando García-Tellado
Dec 20, 2016·Nature Chemical Biology·Ridao ChenFei Sun
Jun 9, 2015·Chemical Communications : Chem Comm·Zhe ZhouMarcus A Tius
Jan 19, 2006·American Journal of Physiology. Renal Physiology·Yun Jung Lee, Ho Jae Han
Nov 23, 2013·Organic & Biomolecular Chemistry·Ivan Franzoni, Clément Mazet
May 1, 2020·Organic & Biomolecular Chemistry·Biswajit RoyDipakranjan Mal
Mar 30, 2021·Bioorganic & Medicinal Chemistry Letters·Patricia MoweryErin T Pelkey
May 13, 2009·The Journal of Organic Chemistry·Reiko UeokaShigeki Matsunaga
Oct 29, 2019·The Journal of Organic Chemistry·Jack Everson, Milton J Kiefel
Feb 15, 2008·Journal of Natural Products·Xuemei NiuIsabel Sattler

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