Synthesis and Biological Evaluation of Novel FtsZ-targeted 3-arylalkoxy-2,6-difluorobenzamides as Potential Antimicrobial Agents

Chem Biol Drug Des. 2016 Feb;87(2):257-64. doi: 10.1111/cbdd.12658. Epub 2015 Sep 28.

Abstract

Novel series of 3-O-arylalkylbenzamide and 3-O-arylalkyl-2,6-difluorobenzamide derivatives were synthesized and evaluated for their on-target activity and antibacterial activity. The results indicated that the 3-O-arylalkyl-2,6-difluorobenzamide derivatives possessed much better on-target activity and antibacterial activity than the 3-O-arylalkylbenzamide derivatives. Among them, 3-O-chlorobenzyl derivative 36 was the most effective in antibacterial activity (0.5, 4, and 8 μg/mL) against Bacillus subtilis ATCC9372, methicillin-resistant Staphylococcus aureus ATCC29213, and penicillin-resistant Staphylococcus aureus PR, while 3-O-methylbenzyl derivative 41 only exhibited the most potent activity (2 μg/mL) against Staphylococcus aureus ATCC25923.

Keywords: 2,6-difluorobenzamide; FtsZ inhibitors; antibacterial activity; on-target activity; synthesis.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Bacillus subtilis / drug effects
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology
  • Drug Resistance, Bacterial / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Infective Agents
  • Benzamides
  • 2,6-difluorobenzamide