Efficacy of phosphonium amphiphilic salts against Acanthamoeba genotype T4

Miloš Lukáč1, Martin Pisárčik1, Mária Garajová2

  • 1Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Kalinčiakova 8, 832 32, Bratislava, Slovakia.

Insights

New phosphonium salts show potent activity against Acanthamoeba, a pathogen causing serious infections like Acanthamoeba keratitis. The compound C16P(Me)2PhBr demonstrated significant trophocidal effects, offering a promising therapeutic candidate.

Area of Science:

  • Microbiology
  • Medicinal Chemistry
  • Parasitology

Background:

  • Acanthamoeba species are opportunistic pathogens responsible for severe human infections such as granulomatous amoebic encephalitis and Acanthamoeba keratitis.
  • Current treatment options for Acanthamoeba infections are limited and challenging.
  • Phosphonium amphiphilic salts have recently emerged as compounds with notable antimicrobial properties.

Purpose of the Study:

  • To evaluate the anti-Acanthamoeba efficacy of a series of 16 synthesized phosphonium salts.
  • To investigate the structure-activity relationship by modifying polar and nonpolar components of the surfactant molecules.
  • To correlate physicochemical properties, such as critical micelle concentration (cmc), with biological activity.

Main Methods:

  • Synthesis and characterization of 16 phosphonium salts with varying alkyl chain lengths and substituents on the phosphorus atom.
  • Determination of physicochemical properties: cmc, surface tension at cmc, and surface area per surfactant head group.
  • Assessment of trophocidal activity against Acanthamoeba quina and Acanthamoeba hatchetti (genotype T4) and evaluation of hemolytic activity against human erythrocytes.

Main Results:

  • The compound C16P(Me)2PhBr exhibited the highest trophocidal activity, with minimal trophocidal concentrations (MTC) of 7.8 μM for A. quina and 15.6 μM for A. hatchetti after 24 hours.
  • The lipophilicity, indicated by cmc values, correlated with the observed biological activities.
  • The efficacy of C16P(Me)2PhBr was found to be comparable or superior to existing treatments for Acanthamoeba keratitis.

Conclusions:

  • Phosphonium amphiphilic salts, particularly C16P(Me)2PhBr, display significant potential as therapeutic agents against Acanthamoeba infections.
  • The structural modifications of these compounds allow for tuning their physicochemical properties and biological activity.
  • C16P(Me)2PhBr represents a promising candidate for developing novel treatments for Acanthamoeba-related diseases.

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