Design and synthesis of paracaseolide A analogues as selective protein tyrosine phosphatase 1B inhibitors

Jian-Peng Yin; Chun-Lan Tang; Li-Xin Gao; Wei-Ping Ma; Jing-Ya Li; Ying Li; Jia Li; Fa-Jun Nan

doi:10.1039/c4ob00214h

Design and synthesis of paracaseolide A analogues as selective protein tyrosine phosphatase 1B inhibitors

Org Biomol Chem. 2014 Jun 7;12(21):3441-5. doi: 10.1039/c4ob00214h. Epub 2014 Apr 22.

Authors

Jian-Peng Yin¹, Chun-Lan Tang, Li-Xin Gao, Wei-Ping Ma, Jing-Ya Li, Ying Li, Jia Li, Fa-Jun Nan

Affiliation

¹ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P.R. China. liying@lzu.edu.cn.

PMID: 24752625
DOI: 10.1039/c4ob00214h

Abstract

A series of structurally related analogues of the natural product paracaseolide A were synthesized and identified as potent PTP1B inhibitors. Among these analogues, compound 10 in particular showed improved PTP1B enzyme inhibitory activity, high selectivity for PTP1B over TC-PTP, and improved cellular effects.

Publication types

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

MeSH terms

4-Butyrolactone / chemical synthesis*
4-Butyrolactone / chemistry
4-Butyrolactone / pharmacology*
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Indicators and Reagents
Insulin / metabolism
Molecular Docking Simulation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Receptor, Insulin / metabolism
Signal Transduction / drug effects

Substances

Enzyme Inhibitors
Indicators and Reagents
Insulin
paracaseolide A
Receptor, Insulin
Protein Tyrosine Phosphatase, Non-Receptor Type 1
4-Butyrolactone