Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action.
Eur J Med Chem
; 135: 1-11, 2017 Jul 28.
Article
in En
| MEDLINE
| ID: mdl-28426995
ABSTRACT
The emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Targeting at the inhibition of bacterial cell division via the control of FtsZ function is one of the effective and promising approaches. Some natural extracts from plants such as sanguinarine and berberine (analogs of pyridinium compounds) are known to alter FtsZ function. In this study, a series of novel quaternary pyridinium compounds was constructed based on the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and their antibacterial activity against nine significant pathogens was investigated using broth microdilution method. In the in vitro assay, the compounds showed strong antibacterial activities against various testing strains, which include some drug-resistant strains such as methicillin-resistant S. aureus and vancomycin-resistant E. faecium. Our results of morphology change of B. subtilis cells and molecular docking proved that the compounds functioned as an effective inhibitor to suppress FtsZ polymerization and FtsZ GTPase activity and thus the compound stops cell division and cause cell death through interacting with C-terminal interdomain cleft of FtsZ.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Methicillin-Resistant Staphylococcus aureus
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Vancomycin-Resistant Enterococci
/
Anti-Bacterial Agents
Language:
En
Journal:
Eur J Med Chem
Year:
2017
Type:
Article
Affiliation country:
Hungary