Identification of caffeoylquinic acid derivatives as natural protein tyrosine phosphatase 1B inhibitors from Artemisia princeps

Jie Zhang; Tatsunori Sasaki; Wei Li; Kazuya Nagata; Koji Higai; Feng Feng; Jian Wang; Maosheng Cheng; Kazuo Koike

doi:10.1016/j.bmcl.2018.02.052

Identification of caffeoylquinic acid derivatives as natural protein tyrosine phosphatase 1B inhibitors from Artemisia princeps

Bioorg Med Chem Lett. 2018 Apr 15;28(7):1194-1197. doi: 10.1016/j.bmcl.2018.02.052. Epub 2018 Mar 6.

Authors

Jie Zhang¹, Tatsunori Sasaki², Wei Li³, Kazuya Nagata², Koji Higai², Feng Feng⁴, Jian Wang⁵, Maosheng Cheng⁵, Kazuo Koike²

Affiliations

¹ Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
² Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
³ Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: liwei@phar.toho-u.ac.jp.
⁴ Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
⁵ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.

PMID: 29525218
DOI: 10.1016/j.bmcl.2018.02.052

Abstract

Considerable attention has been paid to protein tyrosine phosphatase 1B (PTP1B) inhibitors as a potential therapy for diabetes, obesity, and cancer. Ten caffeoylquinic acid derivatives (1-10) from leaves of Artemisia princeps Pamp. (Asteraceae) were identified as natural PTP1B inhibitors. Among them, chlorogenic acid (3) showed the most potent inhibitory activity (IC₅₀ 11.1 μM). Compound 3 was demonstrated to be a noncompetitive inhibitor by a kinetic analysis. Molecular docking simulation suggested that compound 3 bound to the allosteric site of PTP1B. Furthermore, compound 3 showed remarkable selectivity against four homologous PTPs. According to these findings, compound 3 might be potentially valuable for further drug development.

Keywords: Artemisia princeps; Caffeoylquinic acid; Chlorogenic acid; Protein tyrosine phosphatase 1B.

Publication types

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

MeSH terms

Artemisia / chemistry*
Dose-Response Relationship, Drug
Humans
Molecular Docking Simulation
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Quinic Acid / analogs & derivatives*
Quinic Acid / chemical synthesis
Quinic Acid / chemistry
Quinic Acid / pharmacology
Structure-Activity Relationship

Substances

caffeoylquinic acid
Quinic Acid
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1