Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation

被引：90

作者：

Wang, Liang-Liang ^{[1
]}

Battini, Narsaiah ^{[1
,3
]}

Bheemanaboina, Rammohan R. Yadav ^{[1
]}

Zhang, Shao-Lin ^{[2
]}

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, Sch Pharmaceut Sci, Chongqing Key Lab Nat Prod Synth & Drug Res, Chongqing 401331, Peoples R China

[3] CSIR Indian Inst Integrat Med IIIM, Jammu, Jammu & Kashmir, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 167卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Norfloxacin; Thiazole; Antimicrobial; Drug combination; DNA gyrase; Chitin synthase; 2-AMINOTHIAZOLYL QUINOLONES; ANTIMALARIAL ACTIVITY; BIOACTIVE EVALUATION; DNA; ANTIBACTERIAL; INHIBITORS; DISCOVERY; DERIVATIVES; HYBRIDS; MRSA;

D O I：

10.1016/j.ejmech.2019.01.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of aminothiazolyl norfloxacin analogues as a new type of potential antimicrobial agents were synthesized and screened for their antimicrobial activities. Most of the prepared compounds exhibited excellent inhibitory efficiencies. Especially, norfloxacin analogue II-c displayed superior antimicrobial activities against K. pneumoniae and C albicans with MIC values of 0.005 and 0.010 mM to reference drugs, respectively. This compound not only showed broad antimicrobial spectrum, rapid bactericidal efficacy and strong enzymes inhibitory potency including DNA gyrase and chitin synthase (CHS), low toxicity against mammalian cells and no obvious propensity to trigger the development of bacterial resistance, but also exerted efficient membrane permeability, and could effectively intercalate into K. pneumoniae DNA to form a steady supramolecular complex, which might block DNA replication to exhibit their powerful antimicrobial activity. Quantum chemical studies were also performed to explain the high antimicrobial activities. Molecular docking showed that compound II-c could bind with gyrase-DNA and topoisomerase IV-DNA through hydrogen bonds and pi-pi stacking. (C) 2019 Elsevier Masson SAS. All rights reserved.

引用

页码：105 / 123

页数：19

共 61 条

[11] Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergistic effects with clinical drugs and interactions with calf thymus DNA [J].