Creating an antibacterial with in vivo efficacy: synthesis and characterization of potent inhibitors of the bacterial cell division protein FtsZ with improved pharmaceutical properties

J Med Chem. 2010 May 27;53(10):3927-36. doi: 10.1021/jm9016366.

Abstract

3-Methoxybenzamide (1) is a weak inhibitor of the essential bacterial cell division protein FtsZ. Alkyl derivatives of 1 are potent antistaphylococcal compounds with suboptimal drug-like properties. Exploration of the structure-activity relationships of analogues of these inhibitors led to the identification of potent antistaphylococcal compounds with improved pharmaceutical properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Biological Availability
  • Blood Proteins / metabolism
  • Caco-2 Cells
  • Cell Division / drug effects
  • Cell Membrane Permeability
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Hepatocytes / metabolism
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Protein Binding
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / cytology
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Blood Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • PC190723
  • Pyridines
  • Thiazoles