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. 2018 Oct;80:195-203. doi: 10.1016/j.bioorg.2018.06.008. Epub 2018 Jun 5.
A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HRMS spectra. All the newly prepared compounds were screened for their potential protein tyrosine phosphatase inhibitory activities. Bioactive assay manifested that most of the azolyl flavonoids exhibited good protein phosphatase 1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed the best inhibitory activity (IC = 1.6 μM) with 9.9-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated 6a has lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity.
一系列唑基黄酮类化合物通过 NMR、IR、MS 和 HRMS 光谱进行了合成和表征。所有新制备的化合物都进行了潜在蛋白酪氨酸磷酸酶抑制活性的筛选。生物活性测定表明，大多数唑基黄酮类化合物表现出良好的蛋白磷酸酶 1B（PTP1B）抑制活性。特别是，三唑基黄酮 6a 对 PTP1B 的抑制活性最好（IC=1.6μM），对密切相关的 T 细胞蛋白酪氨酸磷酸酶（TCPTP）的选择性为 9.9 倍。细胞活力测定表明 6a 的细胞毒性较低。分子建模和动力学研究揭示了 PTP1B 对 TCPTP 选择性的原因。对这些化合物进行了量子化学研究，以了解对活性至关重要的结构特征。
