The study of 9,10-dihydroacridine derivatives as a new and effective molecular scaffold for antibacterial agent development

Biochem Biophys Res Commun. 2021 Mar 26:546:40-45. doi: 10.1016/j.bbrc.2021.01.096. Epub 2021 Feb 6.

Abstract

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism. Both compounds were found possessing strong antibacterial activity against some selected Gram-positive bacteria including MRSA, VISA and VRE. The biological study suggests that the compounds promoted FtsZ polymerization and also disrupted Z-ring formation at the dividing site and consequently, the bacterial cell division is interrupted and causing cell death.

Keywords: 9,10-Dihydroacridine derivative; Antibacterial activity; Drug-resistant strain; FtsZ inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry*
  • Acridines / pharmacology*
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Cell Division / drug effects
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism
  • Drug Design*
  • Gram-Positive Bacteria / drug effects
  • Methicillin / pharmacology
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects

Substances

  • Acridines
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Methicillin