Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents

  • Loftsson T
  • Thorsteinsson T
  • Másson M
13Citations
Citations of this article
15Readers
Mendeley users who have this article in their library.

Abstract

Quaternary ammonium surfactants, such as benzalkonium chloride and cetylpyridinium chloride, are commonly used as antibacterial agents for disinfectants and for general environmental sanitation, as well as in surfactants, penetration enhancers and preservatives in pharmaceutical and cosmetic formulations. However, these agents are known to cause various side-effects and toxic reactions that are believed to be associated with their chemical stability. Soft analogues of the long-chain quaternary ammonium compounds were synthesized according to the soft drug approach and their physicochemical properties investigated, such as their hydrolytic rate constant, surface activity and lipophilicity. Structure-activity studies showed that the antimicrobial activity of the compounds was strongly influenced by their lipophilicity and chemical stability, the activity increasing with increasing lipophilicity and stability. However, in soft drug design structure-activity relationships are combined with structure-inactivation relationships during the lead optimization. The safety index (SI) of compounds was defined as the hydrolytic rate constant divided by the minimum inhibitory concentration. The SI of the soft antibacterial agents was found to increase with increasing lipophilicity but optimum SI was obtained when their hydrolytic t1/2, at pH 6 and 60°C, was about 11 h. Optimization of the soft antibacterial agents through SI optimization resulted in potent but chemically unstable quaternary ammonium antibacterial agents.

Cite

CITATION STYLE

APA

Loftsson, T., Thorsteinsson, T., & Másson, M. (2010). Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents. Journal of Pharmacy and Pharmacology, 57(6), 721–727. https://doi.org/10.1211/0022357056226

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free