Bromophenols as inhibitors of protein tyrosine phosphatase 1B with antidiabetic properties
Bromophenols as inhibitors of protein tyrosine phosphatase 1B with antidiabetic properties
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DOI：
10.1016/j.bmcl.2012.02.074
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发表时间：
2012-04-15
影响因子：
2.7
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Shi, Dayong;Li, Jing;Wang, Tao
以从红藻Rhodomela confervoides中分离得到的溴苯酚4 e（IC_（50）= 2.42 μ mol/ L）为基础，合成了一系列溴苯酚衍生物，并对其进行了体内外蛋白酪氨酸磷酸酶1B（PTP 1B）抑制剂活性的评价。结果表明，所有合成的化合物在测试浓度下显示出弱至良好的PTP 1B抑制。其中，高度溴化的化合物4g显示出对PTP 1B的有希望的抑制活性，其IC 50为0.68 μ mol/L，比先导化合物4 e强约4倍。此外，化合物4g表现出对其他PTP（TCPTP、LAR、SHP-1和SHP-2）的高选择性。更重要的是，化合物4g的体内抗糖尿病活性研究也显示了令人鼓舞的结果。(C)2012爱思唯尔有限公司保留所有权利。
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 (IC50 = 2.42 mu mol/ 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 IC50 0.68 mu mol/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. (C) 2012 Elsevier Ltd. All rights reserved.