Antibacterial activity of 3-methylbenzo[d]thiazol-methylquinolinium derivatives and study of their action mechanism

Autor: Yuan Yuan Zheng, Wen Chang Yuan, Yu Jing Lu, Sen Yuan Cai, Xiao Mei Li, Ning Sun, Zhi Yuan Fang, Zhihua Liu, Qi Guo, Ruo Lan Du, Kwok Yin Wong, Ting Liu
Rok vydání: 2018
Předmět:
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine
cell division
Cell Survival
medicine.drug_class
Antibiotics
Microbial Sensitivity Tests
01 natural sciences
Bacterial resistance
Cell Line
Vancomycin-Resistant Enterococci
Mice
Structure-Activity Relationship
03 medical and health sciences
antibacterial activity
Drug Discovery
Escherichia coli
medicine
Animals
Humans
FtsZ
FtsZ inhibition
Pharmacology
Cell Death
Dose-Response Relationship
Drug
Molecular Structure
biology
010405 organic chemistry
Chemistry
lcsh:RM1-950
3-methylbenzo[d]thiazol-methylquinolinium derivatives
General Medicine
Combinatorial chemistry
Small molecule
Anti-Bacterial Agents
0104 chemical sciences
Multiple drug resistance
Thiazoles
030104 developmental biology
lcsh:Therapeutics. Pharmacology
Quinolines
biology.protein
Antibacterial activity
Research Paper
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 33, Iss 1, Pp 879-889 (2018)
Journal of Enzyme Inhibition and Medicinal Chemistry
DOI: 10.6084/m9.figshare.6652322
Popis: The increasing incidence of multidrug resistant bacterial infection renders an urgent need for the development of new antibiotics. To develop small molecules disturbing FtsZ activity has been recognized as promising approach to search for antibacterial of high potency systematically. Herein, a series of novel quinolinium derivatives were synthesized and their antibacterial activities were investigated. The compounds show strong antibacterial activities against different bacteria strains including MRSA, VRE and NDM-1 Escherichia coli. Among these derivatives, a compound bearing a 4-fluorophenyl group (A2) exhibited a superior antibacterial activity and its MICs to the drug-resistant strains are found lower than those of methicillin and vancomycin. The biological results suggest that these quinolinium derivatives can disrupt the GTPase activity and dynamic assembly of FtsZ, and thus inhibit bacterial cell division and then cause bacterial cell death. These compounds deserve further evaluation for the development of new antibacterial agents targeting FtsZ.
Databáze: OpenAIRE
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