Light induced antimicrobial properties of a brominated boron difluoride (BF(2)) chelated tetraarylazadipyrromethene photosensitizer

J Med Chem. 2010 Oct 28;53(20):7337-43. doi: 10.1021/jm100585j.

Abstract

Herein we describe a new antimicrobial photodynamic therapeutic (PDT) agent based upon the brominated BF(2) chelated tetraarylazadipyrromethene photosensitizer class. Bis-ammonium salt substitution of the photosensitizer promoted a rapid 10 min uptake into Gram-positive and -negative bacterial strains and pathogenic yeasts. A photosensitizer and light dose response analysis for methicillin-sensitive S. aureus showed an impressive antibacterial efficacy with 1, 2, and 5 μg/mL 6. Specifically, light activation with a dose of 16 J/cm(2) and 5 μg/mL 6 resulted in a 6.8 and 3.4 log(10) reduction of S. aureus and a clinically defined methicillin-resistant Staphylococcus aureus (MRSA) strain, respectively. Encouragingly, a broad spectrum pathogen response (using 5 μg/mL 6 and 75 J/cm(2)) was observed with 3.6 and 5.7 log(10) decreases in viable cell numbers achievable for Gram-negative bacterium E. coli and the pathogenic yeast C. albicans, respectively. The photophysical and cell eradicating characteristics of this bis-cationic PDT agent suggest that it has broad potential in antimicrobial therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology
  • Boron*
  • Candida albicans / drug effects
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Escherichia coli / drug effects
  • Humans
  • Light*
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Boron Compounds
  • Coordination Complexes
  • Photosensitizing Agents
  • Pyrroles
  • Boron