Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Bioorg Med Chem Lett. 2012 Apr 15;22(8):2827-32. doi: 10.1016/j.bmcl.2012.02.074. Epub 2012 Mar 2.
A series of bromophenol derivatives were synthesized and evaluated as protein tyrosine phosphatase 1B (PTP1B) inhibitors in vitro and in vivo based on bromophenol 4e (IC(50)=2.42 μmol/L), which was isolated from red algae Rhodomela confervoides. The results showed that all of the synthesized compounds displayed weak to good PTP1B inhibition at tested concentration. Among them, highly brominated compound 4g exhibited promising inhibitory activity against PTP1B with IC(50) 0.68 μmol/L, which was approximately fourfold more potent than lead compound 4e. Further, compound 4g demonstrated high selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). More importantly, in vivo antidiabetic activities investigations of compound 4g also demonstrated inspiring results.
基于从红藻龙须菜中分离得到的溴酚 4e（IC50=2.42μmol/L），我们合成了一系列溴酚衍生物，并对其进行了体外和体内的蛋白酪氨酸磷酸酶 1B（PTP1B）抑制活性评价。结果表明，在所测试的浓度下，所有合成的化合物均表现出弱至良好的 PTP1B 抑制活性。其中，高度溴化的化合物 4g 对 PTP1B 表现出有前景的抑制活性，IC50为 0.68μmol/L，比先导化合物 4e 约强四倍。此外，化合物 4g 对其他 PTPs（TCPTP、LAR、SHP-1 和 SHP-2）具有很高的选择性。更重要的是，化合物 4g 的体内抗糖尿病活性研究也取得了令人鼓舞的结果。
