School of Pharmacy, Yancheng Teachers' University, Yancheng, Jiangsu 224051, People's Republic of China.
School of Pharmacy, Yancheng Teachers' University, Yancheng, Jiangsu 224051, People's Republic of China.
Bioorg Chem. 2019 Jul;88:102900. doi: 10.1016/j.bioorg.2019.03.074. Epub 2019 Apr 9.
A series of imidazole flavonoids as new type of protein tyrosine phosphatase inhibitors were synthesized and characterized. Most of them gave potent protein phosphatase 1B (PTP1B) inhibitory activities. Especially, compound 11a could effectively inhibit PTP1B with an IC value of 0.63 μM accompanied with high selectivity ratio (9.5-fold) over T-cell protein tyrosine phosphatase (TCPTP). This compound is cell permeable with relatively low cytotoxicity. The high binding affinity and selectivity was disclosed by molecular modeling and dynamics studies. The structural features essential for activity were confirmed by quantum chemical studies.
一系列咪唑黄酮类化合物被合成为新型的蛋白酪氨酸磷酸酶抑制剂，并对其进行了特征描述。它们中的大多数对蛋白磷酸酶 1B（PTP1B）具有很强的抑制活性。特别是，化合物 11a 对 PTP1B 的抑制作用非常有效，IC 值为 0.63 μM，对 T 细胞蛋白酪氨酸磷酸酶（TCPTP）的选择性比值为 9.5 倍。该化合物具有细胞通透性，且细胞毒性相对较低。通过分子建模和动力学研究揭示了其高结合亲和力和选择性。量子化学研究证实了对活性至关重要的结构特征。
