Discovery of novel bromophenol 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isobutoxymethyl)benzyl)benzene-1,2-diol as protein tyrosine phosphatase 1B inhibitor and its anti-diabetic properties in C57BL/KsJ-db/db mice.
Discovery of novel bromophenol 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isobutoxymethyl)benzyl)benzene-1,2-diol as protein tyrosine phosphatase 1B inhibitor and its anti-diabetic properties in C57BL/KsJ-db/db mice.
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DOI：
10.1016/j.ejmech.2013.03.037
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发表时间：
2013-06
影响因子：
6.7
通讯作者：
B. Jiang;Shuju Guo;Dayong Shi;Chaohong Guo;Tao Wang
中科院分区：
文献类型：
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作者：
B. Jiang;Shuju Guo;Dayong Shi;Chaohong Guo;Tao Wang
为了开发新型小分子PTP 1B抑制剂，设计、合成了一系列溴苯酚衍生物，并进行了体内外评价。在20 μg/mL浓度下，所有化合物对PTP 1B均表现出较弱的抑制活性（5.62-96.25%）。在这些化合物中，3，4-二溴-5-（2-溴-3，4-二羟基-6-（异丁氧基甲基）苄基）苯-1，2-二醇（9）表现出比先导化合物BDDPM（IC 50 = 2.42 μM）更强的PTP 1B抑制活性（IC 50 = 1.50 μM），以及对其他PTP（TCPTP、LAR、SHP-1和SHP-2）的高选择性。使用C57 BL/KsJ-db/db小鼠模型的抗糖尿病测定结果表明，化合物9有效降低血糖、总胆固醇和HbA 1c（P < 0.01）。
In an effort to develop novel small molecule PTP1B inhibitors, a series of bromophenol derivatives were designed, synthesized and evaluated in vitro and in vivo. All of the synthesized compounds displayed weak to potent PTP1B inhibitory activities (5.62–96.25%) at 20 μg/mL. Among these compounds, 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isobutoxymethyl)benzyl)benzene-1,2-diol (9) exhibited enhanced PTP1B inhibitory activity (IC50= 1.50 μM) than the lead compound BDDPM (IC50= 2.42 μM) and high selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Results of anti-diabetic assay using C57BL/KsJ-db/db mouse model demonstrated that compound 9 was effective at lowering blood glucose, total cholesterol and HbA1c (P < 0.01).