Mahapatra Manoj Kumar, Kumar Rajnish, Kumar Manoj
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Bioorg Chem. 2017 Apr;71:1-9. doi: 10.1016/j.bioorg.2017.01.007. Epub 2017 Jan 17.
PTP1B (protein tyrosine phosphatase 1B) dephosphorylates the insulin receptor substrate and thus acts as a negative regulator of the insulin and leptin signalling pathway. Recently, it has been considered as a new therapeutic target of intervention for the treatment of type2 diabetes. A series of aryl/alkylsulfonyloxy-5-(3-methoxybenzylidene)thiazolidine-2,4-dione derivatives were synthesized, screened in vitro for their PTP1B inhibitory activity and in vivo for anti-hyperglycaemic activity. Docking results further helped in understanding the nature of interactions governing the binding mode of ligands inside the active site of PTP1B. Among the synthesized compounds, 13 and 16 were found to be potent PTP1B inhibitors having IC of 7.31 and 8.73μM respectively. Significant lowering of blood glucose level was observed in some of the synthesized compounds in in vivo study.
蛋白酪氨酸磷酸酶1B（PTP1B）使胰岛素受体底物去磷酸化，因此作为胰岛素和瘦素信号通路的负调节因子。最近，它被认为是治疗2型糖尿病的一种新的干预治疗靶点。合成了一系列芳基/烷基磺酰氧基-5-（3-甲氧基亚苄基）噻唑烷-2,4-二酮衍生物，在体外筛选它们的PTP1B抑制活性，在体内筛选其抗高血糖活性。对接结果进一步有助于理解决定配体在PTP1B活性位点内结合模式的相互作用性质。在合成的化合物中，发现13和16是有效的PTP1B抑制剂，IC50分别为7.31和8.73μM。在体内研究中，一些合成化合物观察到血糖水平显著降低。
