2,6-Difluorobenzamide Inhibitors of Bacterial Cell Division Protein FtsZ: Design, Synthesis, and Structure–Activity Relationships

Valentina Straniero, Carlo Zanotto, Letizia Straniero, Andrea Casiraghi, Stefano Duga, Antonia Radaelli, Carlo De Giuli Morghen, Ermanno Valoti

Research output: Contribution to journalArticle

Abstract

A wide variety of drug-resistant microorganisms are continuously emerging, restricting the therapeutic options for common bacterial infections. Antimicrobial agents that were originally potent are now no longer helpful, due to their weak or null activity toward these antibiotic-resistant bacteria. In addition, none of the recently approved antibiotics affect innovative targets, resulting in a need for novel drugs with innovative antibacterial mechanisms of action. The essential cell division protein filamentous temperature-sensitive Z (FtsZ) has emerged as a possible target, thanks to its ubiquitous expression and its homology to eukaryotic β-tubulin. In the latest years, several compounds were shown to interact with this prokaryotic protein and selectively inhibit bacterial cell division. Recently, our research group developed interesting derivatives displaying good antibacterial activities against methicillin-resistant Staphylococcus aureus, as well as vancomycin-resistant Enterococcus faecalis and Mycobacterium tuberculosis. The aim of the present study was to summarize the structure–activity relationships of differently substituted heterocycles, linked by a methylenoxy bridge to the 2,6-difluorobenzamide, and to validate FtsZ as the real target of this class of antimicrobials.

Original languageEnglish
Pages (from-to)1303-1318
Number of pages16
JournalChemMedChem
Volume12
Issue number16
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • 2,6-difluorobenzamides
  • antibiotics
  • antimicrobial resistance
  • FtsZ
  • inhibitors
  • MRSA

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Fingerprint Dive into the research topics of '2,6-Difluorobenzamide Inhibitors of Bacterial Cell Division Protein FtsZ: Design, Synthesis, and Structure–Activity Relationships'. Together they form a unique fingerprint.

  • Cite this

    Straniero, V., Zanotto, C., Straniero, L., Casiraghi, A., Duga, S., Radaelli, A., De Giuli Morghen, C., & Valoti, E. (2017). 2,6-Difluorobenzamide Inhibitors of Bacterial Cell Division Protein FtsZ: Design, Synthesis, and Structure–Activity Relationships. ChemMedChem, 12(16), 1303-1318. https://doi.org/10.1002/cmdc.201700201