Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action

Senyuan Cai, Wenchang Yuan, Ying Li, Xuanhe Huang, Qi Guo, Ziwei Tang, Zhiyuan Fang, Hai Lin, Wing Leung Wong, Kwok Yin Wong, Yu Jing Lu, Ning Sun

Research output: Journal article publicationJournal articleAcademic researchpeer-review

11 Citations (Scopus)

Abstract

Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In the present study, a series of 1-methylquinolinium derivatives, which were integrated with an indole fragment at its 2-position and a variety of amino groups (cyclic or linear, mono- or di-amine) at the 4-position were synthesized and their antibacterial activities were evaluated. The results of antibacterial study show that the representative compounds can effectively inhibit the growth of testing strains including MRSA and VRE, with MIC values of 1–4 μg/mL by bactericidal mode. The mode of action assays revealed that c2 can effectively disrupt the rate of GTP hydrolysis and dynamic polymerization of FtsZ, and thus inhibits bacterial cell division and then causes bacterial cell death. In addition, the result of resistance generation experiment reveals that c2 is not likely to induce resistance in S. aureus.

Original languageEnglish
Pages (from-to)1274-1282
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume27
Issue number7
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • Antibacterial activity
  • Cells division
  • Drug resistant bacteria
  • FtsZ
  • Indolyl quinolinium derivatives

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this