Design, synthesis of novel azolyl flavonoids and their protein tyrosine Phosphatase-1B inhibitory activities

被引：18

作者：

Zhang, Ling ^{[1
]}

Ge, Yu ^{[1
]}

Song, Hao Ming ^{[1
]}

Wang, Qing Ming ^{[1
]}

Zhou, Cheng-He ^{[2
]}

机构：

[1] Yancheng Teachers Univ, Sch Pharm, Yancheng 224051, Jiangsu, Peoples R China

[2] Southwest Univ, Sch Chem & Chem Engn, Lab Bioorgan & Med Chem, Chongqing 400715, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2018年 / 80卷

关键词：

Flavonoid; Azole; Protein tyrosine phosphatase; Selectivity; Cell viability; 1B INHIBITORS; PTP1B INHIBITORS; POTENT; DERIVATIVES; DISCOVERY; PERMEABILITY; BROMOPHENOL; DOCKING; ANALOGS; GLUCOSE;

D O I：

10.1016/j.bioorg.2018.06.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HAMS 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 (IC50 = 1.6 mu M) 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.

引用

页码：195 / 203

页数：9

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