pmid: 31742469,   nlmid 101150203,  doi:10.1080/14756366.2019.1690481

Design and synthesis of tricyclic terpenoid derivatives as novel PTP1B inhibitors with improved pharmacological property and in vivo antihyperglycaemic efficacy.

Yang, Lingling Chen, Feng Gao, Cheng Chen, Jiabao Li, Junyan Liu, Siyan Zhang, Yuanyuan Wang, Zhouyu Qian, Shan

Vol. 35, Issue 35, Dec.2020

Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem),  ISSN 1475-6374


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 with PTP1B inhibitory activity has been reported. However, has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds , and exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 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.

MESH Headings

Article Keywords

Protein tyrosine phosphatase 1B | antihyperglycaemic effect | insulin-resistant | oleanolic acid | type 2 diabetes |


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