Design, synthesis and biological evaluation of novel diaryl ethers bearing a pyrimidine motif as human Pin1 inhibitors.
- Author:
Yue-Yue XI
1
;
Jing JIN
;
Yan SUN
;
Xiao-Guang CHEN
;
Hong-Rui SONG
;
Bai-Ling XU
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Drug Design;
Enzyme Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Ethers;
chemical synthesis;
chemistry;
pharmacology;
Humans;
Inhibitory Concentration 50;
Molecular Docking Simulation;
Molecular Structure;
NIMA-Interacting Peptidylprolyl Isomerase;
Peptidylprolyl Isomerase;
antagonists & inhibitors;
metabolism;
Pyrimidines;
chemistry;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2013;48(8):1266-1272
- CountryChina
- Language:Chinese
-
Abstract:
Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.
