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

Autor: Wang LL; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China., Battini N; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China., Bheemanaboina RRY; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China., Zhang SL; School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331, PR China. Electronic address: zhangsl@cqu.edu.cn., Zhou CH; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address: zhouch@swu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2019 Apr 01; Vol. 167, pp. 105-123. Date of Electronic Publication: 2019 Feb 04.
DOI: 10.1016/j.ejmech.2019.01.072
Abstrakt: 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 π-π stacking.
(Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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