title: Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B.
abstract: By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by ¹H-NMR,13C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had good activities against PTP1B. Among them, compound29(IC50= 0.91 ± 0.33 μM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound29was identified as a competitive inhibitor of PTP1B with aKivalue of 0.78 μM in enzyme kinetic studies.
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China. hehaibing@ntu.edu.cn.
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. geyinghua1992@163.com.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ge
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China. dai_hong@aliyun.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China. cuisong123@163.com.
authors.forename: Song
authors.initials: S
authors.lastname: Cui
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China. yefei@zstu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China. aukaukauk@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Jin
authors.affiliation: College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China. ntushyj@163.com.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shi
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D008095:Lithocholic Acid / Q000737:chemistry; D013058:Mass Spectrometry; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D066244:Proton Magnetic Resonance Spectroscopy; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007555:Isoxazoles; D013267:Stilbenes; D008095:Lithocholic Acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: inhibitor; lithocholic acid; protein tyrosine phosphatase 1B (PTP1B); stilbene