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Author Spotlight: Studying Behavior of Acanthamoeba to Develop Targeted Strategies for Preventing Acanthamoeba Keratitis
Published on: September 20, 2024
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.
Abstract:
Acanthamoebae are opportunistic pathogens causing serious human infections, including granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The treatment of those infections is limited and difficult to date. Recent research demonstrated high antimicrobial activity of phosphonium amphiphilic salts. In the present work we aimed to investigate the anti-Acanthamoeba effect of a series of 16 phosphonium salts. The structure of these synthesized cationic amphiphiles was modified in both the polar and nonpolar parts of the surfactant molecule. The compounds have different alkyl chain lengths (C12 - C18) and different numbers of methyl and phenyl groups (0 - 3) attached to the quaternary phosphorus atom. The following basic physicochemical properties of the compounds were determined: critical micelle concentration (cmc), the surface tension value at the cmc and the surface area per surfactant head group. The cmc values, which express the degree of lipophilicity of compounds, were correlated with biological activities. The effects of phosphonium salts on trophozoites of Acanthamoeba quina and Acanthamoeba hatchetti (both strains of genotype T4) and human erythrocytes were studied. The highest trophocidal activity was recorded for the compound C16P(Me)2PhBr with the minimal trophocidal concentration (MTC) of 7.8 μM for the A. quina strain and 15.6 μM for the A. hatchetti strain, after 24 h. Its activity was comparable or higher than the activity of drugs currently used in the treatment of Acanthamoeba keratitis. Therefore, this compound is a promising candidate in the fight against infections caused by Acanthamoeba.
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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