Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties.

Vadim V Ermolaev,Daria M Arkhipova,Anna P Lyubina,Vasili A Miluykov,Natalia V Kulik,Syumbelya K Amerhanova,Alexandra D Voloshina,Valentine P Ananikov

doi:10.3390/ijms23010086

Abstract

Structure–activity relationships are important for the design of biocides and sanitizers. During the spread of resistant strains of pathogenic microbes, insights into the correlation between structure and activity become especially significant. The most commonly used biocides are nitrogen-containing compounds; the phosphorus-containing ones have been studied to a lesser extent. In the present study, a broad range of sterically hindered quaternary phosphonium salts (QPSs) based on tri-tert-butylphosphine was tested for their activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans, Trichophyton mentagrophytes var. gypseum). The cation structure was confirmed to determine their biological activity. A number of QPSs not only exhibit high activity against both Gram-positive and -negative bacteria but also possess antifungal properties. Additionally, the hemolytic and cytotoxic properties of QPSs were determined using blood and a normal liver cell line, respectively. The results show that tri-tert-butyl(n-dodecyl)phosphonium and tri-tert-butyl(n-tridecyl)phosphonium bromides exhibit both low cytotoxicity against normal human cells and high antimicrobial activity against bacteria, including methicillin-resistant strains S. aureus (MRSA). The mechanism of QPS action on microbes is discussed. Due to their high selectivity for pathogens, sterically hindered QPSs could serve as effective tunable biocides.

Highlights

The widespread use of antibiotics for the treatment of various diseases of nonbacterial etiology and other forms of misuse have led to the appearance of bacterial pathogens that are resistant to many well-known antibiotics [1,2,3,4]
The study of the mechanism of action is one of the most important stages in the inTherefore, we studied the membranotropic effect of the quaternary phosphonium salts (QPSs) on the absorption of the vestigation of new antimicrobial agents
The phosphonium compounds with 14–16 methylene fragments in the alkyl chain were the most effective in inhibiting the growth of Gram-negative bacteria

Summary

Introduction

The widespread use of antibiotics for the treatment of various diseases of nonbacterial etiology and other forms of misuse have led to the appearance of bacterial pathogens that are resistant to many well-known antibiotics [1,2,3,4]. In the case of cationic surfactants, the determinative factors are the charge, the number of cationic centers, the nature of the counter-ion, and the length/number of alkyl substituents and aromatic groups [15]. These structure features regulate the self-organization of the surfactants, increasing the local concentrations and cationic charges of amphiphiles on bacteria. The so-called “cut-off effect” in a homologous series of surfactants with long hydrocarbon chains should be noted: as the chain length increases, the biological activity of the compounds increases up to a critical point, beyond which the activity is lost [16]

Methods

Results

Conclusion