title: Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on α-glucosidase.
abstract: In this study, eight quinazolinone derivatives were designed and synthesized. Their inhibitory activities on α-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 α-glucosidase with IC50values of 12.5±0.1μM and 15.6±0.2μM, respectively. Spectroscopy methods were performed to analyze the inhibitory mechanisms of both compounds on α-glucosidase. The results revealed that they reversibly inhibited α-glucosidase in a non-competitive manner. CQ and BQ could statically quench the fluorescence spectra by formation of an inhibitor-α-glucosidase complex. The interaction between CQ and α-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 α-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.
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
authors.forename: Mankun
authors.initials: M
authors.lastname: Wei
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China. Electronic address: chaiweiming@jxnu.edu.cn.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chai
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China. Electronic address: yypeng@jxnu.edu.cn.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Peng
mesh_terms: D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D052999:Quinazolinones; D000520:alpha-Glucosidases
keywords: Docking; Fluorescence; Quinazolinone; α-Glucosidase