Evaluation of the antibacterial efficacy of diesters of azelaic acid

Eur J Pharm Sci. 2004 Apr;21(5):589-96. doi: 10.1016/j.ejps.2003.12.006.

Abstract

A number of diesters of the topical dermatosis treatment azelaic (nonanedioic) acid were prepared and tested for antibacterial effect. Two esters, bis-[(hexanoyloxy)methyl] nonanedioate and especially bis-[(butanoyloxy)methyl] nonanedioate showed promising activity against acne related bacteria in vitro. No activity of azelaic acid was detected in Mueller Hinton II agar at pH 7.3 when using the agar diffusion method, whereas both esters gave zones of growth inhibition. At pH 5.6, activity of azelaic acid was detected. At this pH, the zones of inhibition and MIC values obtained with azelaic acid were smaller than those of bis-[(butanoyloxy)methyl] nonanedioate for all test organisms. A preparation for topical use containing 20% (w/w) bis-[(butanoyloxy)methyl] nonanedioate, and the commercially available Skinoren (20% (w/w) azelaic acid), were compared for antibacterial effect against cutaneous bacteria using contact plate analyses of the skin. Though Skinoren was usually most effective, the differences were not statistically significant. Furthermore, bacteria surviving contact with the topical preparations were invariably more sensitive to the ester than to azelaic acid upon subculturing onto agar (pH 5.6) containing either preparation at 0.2-0.7 mg/ml. This might indicate that other factors, such as the composition of the cream base, mitigate the antibacterial activity of the ester. It is proposed that the pharmacological and microbiological properties of bis-[(butanoyloxy)methyl] nonanedioate are worthy of further study based on an extended screening of acne sufferers.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Dicarboxylic Acids / chemistry*
  • Dicarboxylic Acids / pharmacology*
  • Drug Evaluation, Preclinical / methods
  • Microbial Sensitivity Tests
  • Propionibacterium acnes / drug effects
  • Propionibacterium acnes / growth & development
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / growth & development

Substances

  • Anti-Bacterial Agents
  • Dicarboxylic Acids
  • azelaic acid