Design, synthesis and in vitro activity of phidianidine B derivatives as novel PTP1B inhibitors with specific selectivity

Li Zhang; Cheng-Shi Jiang; Li-Xin Gao; Jing-Xu Gong; Zhong-Hua Wang; Jing-Ya Li; Jia Li; Xu-Wen Li; Yue-Wei Guo

doi:10.1016/j.bmcl.2015.12.097

Design, synthesis and in vitro activity of phidianidine B derivatives as novel PTP1B inhibitors with specific selectivity

Bioorg Med Chem Lett. 2016 Feb 1;26(3):778-781. doi: 10.1016/j.bmcl.2015.12.097. Epub 2015 Dec 29.

Authors

Li Zhang¹, Cheng-Shi Jiang², Li-Xin Gao¹, Jing-Xu Gong¹, Zhong-Hua Wang³, Jing-Ya Li¹, Jia Li¹, Xu-Wen Li⁴, Yue-Wei Guo⁵

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
² State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China; School of Biological Science and Technology, University of Jinan, 336, Nan Xin Zhuang Xi Road, Jinan, Shandong 250022, PR China.
³ School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Hai Quan Road, Fengxian Dictrict, Shanghai 201418, PR China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Electronic address: [email protected].
⁵ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Electronic address: [email protected].

PMID: 26774579
DOI: 10.1016/j.bmcl.2015.12.097

Abstract

A series of phidianidine B derivatives were synthesized by introducing various heterocyclic rings. Their inhibitory effects on PTP1B and other PTPs (TCPTP, SHP1, SHP2 and LAR) were evaluated. A majority of them displayed significant inhibitory potency and specific selectivity over PTP1B. The SAR and molecular docking analysis were also described.

Keywords: Docking analysis; Function-oriented synthesis; Oxadiazole derivative; PTP1B inhibitor; Phidianidine; Specific selectivity.

Publication types

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

MeSH terms

Binding Sites
Catalytic Domain
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Humans
Indole Alkaloids / chemistry*
Inhibitory Concentration 50
Molecular Docking Simulation
Oxadiazoles / chemistry*
Protein Binding
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Indole Alkaloids
Oxadiazoles
phidianidine B
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1