Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on α-glucosidase

被引：73

作者：

Wei, Mankun ^{[1
,2
]}

Chai, Wei-Ming ^{[1
,2
]}

Wang, Rui ^{[1
,2
]}

Yang, Qin ^{[1
,2
]}

Deng, Zhihong ^{[3
]}

Peng, Yiyuan ^{[1
,2
]}

机构：

[1] Minist Educ, Key Lab Small Fuct Organ Mol, Nanchang 330022, Jiangxi, Peoples R China

[2] Jiangxi Normal Univ, Coll Life Sci, Nanchang 330022, Jiangxi, Peoples R China

[3] Key Lab Green Chem, Nanchang, Jiangxi, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Quinazolinone; alpha-Glucosidase; Fluorescence; Docking; MEDICINAL CHEMISTRY; DISEASE; WATER;

D O I：

10.1016/j.bmc.2016.09.042

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：

In this study, eight quinazolinone derivatives were designed and synthesized. Their inhibitory activities on alpha-glucosidase were assessed in vitro. Two compounds: 2-(4-chlorophenyl)-quinazolin-4(3H)-one (CQ) and 2-(4-bromophenyl)-quinazolin-4(3H)-one (BQ) were found to be potent inhibitors of alpha-glucosidase with IC50 values of 12.5 +/- 0.1 mu M and 15.6 +/- 0.2 mu M, respectively. Spectroscopy methods were performed to analyze the inhibitory mechanisms of both compounds on alpha-glucosidase. The results revealed that they reversibly inhibited alpha-glucosidase in a non-competitive manner. CQ and BQ could statically quench the fluorescence spectra by formation of an inhibitor-alpha-glucosidase complex. The interaction between CQ and alpha-glucosidase depended on hydrogen bonds, electrostatic and hydrophobic force, while the driving force of the binding between BQ and the enzyme was hydrophobic. The docking results showed that BQ was less active than CQ against alpha-glucosidase because of its weaker interaction with the enzyme. In brief, the quinazolinone derivatives identified in this work were potentially promising candidates for developing as novel anti-diabetic agents. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1303 / 1308

页数：6

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