Synthesis, biological evaluation, and molecular docking study of novel allyl-retrochalcones as a new class of protein tyrosine phosphatase 1B inhibitors
Synthesis, biological evaluation, and molecular docking study of novel allyl-retrochalcones as a new class of protein tyrosine phosphatase 1B inhibitors
复制标题
新型蛋白酪氨酸磷酸酶1B抑制剂新型烯丙基逆查尔酮的合成、生物学评价及分子对接研究
DOI：
10.1016/j.bmc.2019.01.034
复制
发表时间：
2019
影响因子：
3.5
通讯作者：
Cheon Seung Hoon
中科院分区：
文献类型：
--
作者：
Zhao Yunjie;Cao Yongkai;Chen Huizhen;Zhuang Fei;Wu Chao;Yoon Goo;Zhu Weiwei;Su Ying;Zheng Suqing;Liu Zhiguo;Cheon Seung Hoon
We describe herein the design, synthesis, and biological evaluation of a series of novel protein tyrosine phosphatase 1B (PTP1B) inhibitor retrochalcones having an allyl chain at the C-5 position of their B ring. Biological screening results showed that the majority of these compounds exhibited an inhibitory activity against PTP1B. Thus, preliminary structure-activity relationship (SAR) and quantitative SAR analyses were conducted. Among the compounds,23was the most potent inhibitor, exhibiting the highestin vitroinhibitory activity against PTP1B with an IC50of 0.57 µM. Moreover, it displayed a significant hepatoprotective property via activation of the IR pathway in type 2 diabetic db/db mice. In addition, the results of our docking study showed that23,as a specific inhibitor of PTP1B, effectively transformed the WPD loop from “close” to “open” in the active site. These results may reveal suitable compounds for the development of PTP1B inhibitors.
