Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy
Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cyto...
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Taylor & Francis Group
2020-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1690481 |
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doaj-7b7c47eabaf2438aae0c8d531db1a2dd2021-07-15T13:10:31ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-0135115216410.1080/14756366.2019.16904811690481Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacyLingling Yang0Feng Chen1Cheng Gao2Jiabao Chen3Junyan Li4Siyan Liu5Yuanyuan Zhang6Zhouyu Wang7Shan Qian8Department of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityDepartment of Chemistry, College of Science, Xihua UniversityDepartment of Chemistry, College of Science, Xihua UniversityDepartment of Pharmaceutical Engineering, College of Food and Bioengineering, Xihua UniversityOverexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide–streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.http://dx.doi.org/10.1080/14756366.2019.1690481protein tyrosine phosphatase 1boleanolic acidinsulin-resistantantihyperglycaemic effecttype 2 diabetes |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Lingling Yang Feng Chen Cheng Gao Jiabao Chen Junyan Li Siyan Liu Yuanyuan Zhang Zhouyu Wang Shan Qian |
| spellingShingle |
Lingling Yang Feng Chen Cheng Gao Jiabao Chen Junyan Li Siyan Liu Yuanyuan Zhang Zhouyu Wang Shan Qian Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy Journal of Enzyme Inhibition and Medicinal Chemistry protein tyrosine phosphatase 1b oleanolic acid insulin-resistant antihyperglycaemic effect type 2 diabetes |
| author_facet |
Lingling Yang Feng Chen Cheng Gao Jiabao Chen Junyan Li Siyan Liu Yuanyuan Zhang Zhouyu Wang Shan Qian |
| author_sort |
Lingling Yang |
| title |
Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| title_short |
Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| title_full |
Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| title_fullStr |
Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| title_full_unstemmed |
Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| title_sort |
design and synthesis of tricyclic terpenoid derivatives as novel ptp1b inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy |
| publisher |
Taylor & Francis Group |
| series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
| issn |
1475-6366 1475-6374 |
| publishDate |
2020-01-01 |
| description |
Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide–streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D. |
| topic |
protein tyrosine phosphatase 1b oleanolic acid insulin-resistant antihyperglycaemic effect type 2 diabetes |
| url |
http://dx.doi.org/10.1080/14756366.2019.1690481 |
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