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

被引:43
作者
Braña, MF [1 ]
García, ML
López, B
de Pascual-Teresa, B
Ramos, A
Pozuelo, JM
Domínguez, MT
机构
[1] Univ San Pablo CEU, Fac CC Expt & Salud, Dept CC Quim, Madrid 28668, Spain
[2] Univ San Pablo CEU, Fac CC Expt & Salud, Dept Biol, Madrid 28668, Spain
关键词
D O I
10.1039/b403052d
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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.
引用
收藏
页码:1864 / 1871
页数:8
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