Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B
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 wer...
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MDPI AG
2016-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/12/1722 |
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doaj-2229f6fef16948dea5cafb522f22b28a2020-11-24T21:56:40ZengMDPI AGMolecules1420-30492016-12-012112172210.3390/molecules21121722molecules21121722Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1BHaibing He0Yinghua Ge1Hong Dai2Song Cui3Fei Ye4Jia Jin5Yujun Shi6College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, ChinaCollege of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, ChinaCollege of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, ChinaCollege of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, ChinaCollege of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, ChinaBy 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, compound 29 (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. Compound 29 was identified as a competitive inhibitor of PTP1B with a Ki value of 0.78 μM in enzyme kinetic studies.http://www.mdpi.com/1420-3049/21/12/1722protein tyrosine phosphatase 1B (PTP1B)lithocholic acidstilbeneinhibitor |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Haibing He Yinghua Ge Hong Dai Song Cui Fei Ye Jia Jin Yujun Shi |
| spellingShingle |
Haibing He Yinghua Ge Hong Dai Song Cui Fei Ye Jia Jin Yujun Shi Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B Molecules protein tyrosine phosphatase 1B (PTP1B) lithocholic acid stilbene inhibitor |
| author_facet |
Haibing He Yinghua Ge Hong Dai Song Cui Fei Ye Jia Jin Yujun Shi |
| author_sort |
Haibing He |
| title |
Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B |
| title_short |
Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B |
| title_full |
Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B |
| title_fullStr |
Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B |
| title_full_unstemmed |
Design, Synthesis and Biological Evaluation of Stilbene Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B |
| title_sort |
design, synthesis and biological evaluation of stilbene derivatives as novel inhibitors of protein tyrosine phosphatase 1b |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2016-12-01 |
| description |
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, compound 29 (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. Compound 29 was identified as a competitive inhibitor of PTP1B with a Ki value of 0.78 μM in enzyme kinetic studies. |
| topic |
protein tyrosine phosphatase 1B (PTP1B) lithocholic acid stilbene inhibitor |
| url |
http://www.mdpi.com/1420-3049/21/12/1722 |
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