Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action

Ning Sun, Ruo Lan Du, Yuan Yuan Zheng, Bao Hua Huang, Qi Guo, Rui Fang Zhang, Kwok Yin Wong, Yu Jing Lu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

42 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume135
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Antibacterial activity
  • Bacterial resistance
  • FtsZ inhibition
  • N-methylbenzofuro[3,2-b]quinolone derivatives
  • N-methylbenzoindolo[3,2-b]quinoline derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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