Synthesis and biological evaluation of tryptophan-derived rhodanine derivatives as PTP1B inhibitors and anti-bacterial agents

Hongyan Liu; Danwen Sun; Hang Du; Changji Zheng; Jingya Li; Huri Piao; Jia Li; Liangpeng Sun

doi:10.1016/j.ejmech.2019.03.059

Synthesis and biological evaluation of tryptophan-derived rhodanine derivatives as PTP1B inhibitors and anti-bacterial agents

Eur J Med Chem. 2019 Jun 15:172:163-173. doi: 10.1016/j.ejmech.2019.03.059. Epub 2019 Mar 30.

Authors

Hongyan Liu¹, Danwen Sun², Hang Du¹, Changji Zheng¹, Jingya Li³, Huri Piao⁴, Jia Li⁵, Liangpeng Sun⁶

Affiliations

¹ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133000, PR China.
² College of Chemistry and Molecular Engineering, East China of Normal University, 3663 Zhongshan North Road, Shanghai, 200062, China.
³ National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, 201203, China.
⁴ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133000, PR China. Electronic address: piaohr@ybu.edu.cn.
⁵ National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: jli@simm.ac.cn.
⁶ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133000, PR China; College of Medicine, Yanbian University, Yanji, 133000, PR China. Electronic address: lpsun@ybu.edu.cn.

PMID: 30978561
DOI: 10.1016/j.ejmech.2019.03.059

Abstract

Several series of novel tryptophan-derived rhodanine derivatives were synthesized and identified as potential competitive PTP1B inhibitors and antibacterial agents. Among the compounds studied, 10b was found to have the best in vitro inhibition activity against PTP1B (IC₅₀ = 0.36 ± 0.02 μM). In addition, the compounds also showed potent inhibition against other PTPs, especially CDC25B. Molecular docking analysis demonstrated that compounds 7c and 10b could occupy both the catalytic site and the adjacent pTyr binding site simultaneously. The compounds also showed higher levels of activity against gram-positive strains, the gram-negative strain Escherichia coli 1924, and multidrug-resistant gram-positive bacterial strains. Compounds 7c, 8c, 9e, 10a, and 10c had comparable or more potent antibacterial activity than the positive controls.

Keywords: Anti-bacterial; PTP1B inhibitor; SAR; Tryptophan-derived rhodanine.

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Multiple, Bacterial / drug effects
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Microbial Sensitivity Tests
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Rhodanine / chemical synthesis
Rhodanine / chemistry
Rhodanine / pharmacology*
Structure-Activity Relationship
Tryptophan / chemistry
Tryptophan / pharmacology*

Substances

Anti-Bacterial Agents
Enzyme Inhibitors
Rhodanine
Tryptophan
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1