Quinazolinone azolyl ethanols: potential lead antimicrobial agents with dual action modes targeting MRSA DNA

被引：60

作者：

Peng, Xin-Mei ^{[1
]}

Peng, Li-Ping ^{[1
]}

Li, Shuo ^{[2
]}

Avula, Srinivasa Rao ^{[1
]}

Kannekanti, Vijaya Kumar ^{[1
]}

Zhang, Shao-Lin ^{[3
]}

Tam, Kin Yip ^{[3
]}

Zhou, Cheng-He ^{[1
]}

机构：

[1] Southwest Univ, Sch Chem & Chem Engn, Inst Bioorgan & Med Chem, Key Lab Appl Chem Chongqing Municipal, Chongqing 400715, Peoples R China

[2] Chongqing Univ Technol, Sch Chem Engn, Chongqing 400054, Peoples R China

[3] Univ Macau, Fac Hlth Sci, Drug Dev Core, Macau, Peoples R China

来源：

FUTURE MEDICINAL CHEMISTRY | 2016年 / 8卷 / 16期

基金：

中国国家自然科学基金;

关键词：

antibacterial; antifungal; DNA cleavage; DNA intercalation; imidazole; quinazolinone; triazole; CALF THYMUS DNA; HUMAN SERUM-ALBUMIN; BIOLOGICAL EVALUATION; ANTIFUNGAL AGENTS; ANTIBACTERIAL AGENTS; BIOACTIVE EVALUATION; DESIGN; QUINOLONE; DERIVATIVES; INHIBITORS;

D O I：

10.4155/fmc-2016-0002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Due to bacterial drug resistance, a new series of quinazolinone azolyl ethanols were synthesized and evaluated. Results: In vitro antibacterial assay showed that triazolyl ethanol quinazolinone 3a was the most active compound, especially against MRSA with minimal inhibitory concentration value of 8 mu g/ml, which was superior to chloromycin and comparable to norfloxacin. Molecular docking study displayed that compound 3a could interact with MRSA DNA by the formation of hydrogen bonds. Further interactions of quinazolinone 3a with MRSA DNA suggested that it could intercalate into MRSA DNA to form 3a-DNA complex. DNA cleavage properties of 3a-Cu2+ and 3a-Zn2+ complexes were confirmed by agarose gel electrophoresis experiments. Conclusion: Compound 3a should be a potential lead antibacterial molecule with dual action modes.

引用

页码：1927 / 1940

页数：14

共 48 条

[21] Molecular Spectroscopy Evidence of Berberine Binding to DNA: Comparative Binding and Thermodynamic Profile of Intercalation [J].