Synthesis, self-aggregation and biological properties of alkylphosphocholine and alkylphosphohomocholine derivatives of cetyltrimethylammonium bromide, cetylpyridinium bromide, benzalkonium bromide (C16) and benzethonium chloride

Eur J Med Chem. 2013 Aug:66:46-55. doi: 10.1016/j.ejmech.2013.05.033. Epub 2013 Jun 3.

Abstract

A series of alkylphosphocholine and alkylphosphohomocholine derivatives of cetyltrimethylammonium bromide, cetylpyridinium bromide, benzalkonium bromide (C16) and benzethonium chloride have been synthesized. Their physicochemical properties were also investigated. The critical micelle concentration (cmc), the surface tension value at the cmc (γcmc), and the surface area at the surface saturation per head group (Acmc) were determined by means of surface tension measurements. The prepared compounds exhibit significant cytotoxic, antifungal and antiprotozoal activities. Alkylphosphocholines and alkylphosphohomocholines possess higher antifungal activity against Candida albicans in comparison with quaternary ammonium compounds in general. However, quaternary ammonium compounds exhibit significantly higher activity against human tumor cells and pathogenic free-living amoebae Acanthamoeba lugdunensis and Acanthamoeba quina compared to alkylphosphocholines. The relationship between structure, physicochemical properties and biological activity of the tested compounds is discussed.

Keywords: Acanthamoeba; Alkylphosphocholines; Candida albicans; Critical micelle concentration; Cytotoxic activity; Quaternary ammonium compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzalkonium Compounds / chemistry*
  • Benzethonium / chemistry*
  • Candida albicans / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cetrimonium
  • Cetrimonium Compounds / chemistry*
  • Cetylpyridinium / chemistry*
  • Chemistry Techniques, Synthetic
  • Humans
  • Micelles
  • Phosphorylcholine / chemical synthesis*
  • Phosphorylcholine / chemistry
  • Phosphorylcholine / pharmacology*
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Benzalkonium Compounds
  • Cetrimonium Compounds
  • Micelles
  • Phosphorylcholine
  • Benzethonium
  • Cetylpyridinium
  • Cetrimonium