Synthesis and biological evaluation of novel human Pin1 inhibitors with benzophenone skeleton

Chang Liu; Jing Jin; Liang Chen; Jie Zhou; Xiaoguang Chen; Decai Fu; Hongrui Song; Bailing Xu

doi:10.1016/j.bmc.2012.03.005

Synthesis and biological evaluation of novel human Pin1 inhibitors with benzophenone skeleton

Bioorg Med Chem. 2012 May 1;20(9):2992-9. doi: 10.1016/j.bmc.2012.03.005. Epub 2012 Mar 9.

Authors

Chang Liu¹, Jing Jin, Liang Chen, Jie Zhou, Xiaoguang Chen, Decai Fu, Hongrui Song, Bailing Xu

Affiliation

¹ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

PMID: 22459212
DOI: 10.1016/j.bmc.2012.03.005

Abstract

A series of novel benzophenone derivatives were prepared and their inhibitory activities were evaluated on hPin1. Of all the synthesized compounds, the most active compound displayed inhibitory activities with an IC(50) value of 5.99 μmol/L. Preliminary structure-activity relationships were analyzed in details and the binding mode of the titled compounds was predicted using FlexX algorithm. The results of this research will shed light on further design and optimization of novel small molecule Pin1 inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Benzophenones / chemical synthesis
Benzophenones / chemistry*
Binding Sites
Computer Simulation
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Humans
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase / antagonists & inhibitors*
Peptidylprolyl Isomerase / genetics
Peptidylprolyl Isomerase / metabolism
Protein Structure, Tertiary
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Structure-Activity Relationship

Substances

Benzophenones
Enzyme Inhibitors
NIMA-Interacting Peptidylprolyl Isomerase
Recombinant Proteins
benzophenone
PIN1 protein, human
Peptidylprolyl Isomerase