Structure-Activity Relationships of the Imidazolium Compounds as Antibacterials of Staphylococcus aureus and Pseudomonas aeruginosa.

Łukasz Pałkowski,Roman Słowiński,Maciej Karolak,Jerzy Błaszczyński,Jerzy Krysiński

doi:10.3390/ijms22157997

Abstract

This paper presents the results of structure–activity relationship (SAR) studies of 140 3,3’-(α,ω-dioxaalkan)bis(1-alkylimidazolium) chlorides. In the SAR analysis, the dominance-based rough set approach (DRSA) was used. For analyzed compounds, minimum inhibitory concentration (MIC) against strains of Staphylococcus aureus and Pseudomonas aeruginosa was determined. In order to perform the SAR analysis, a tabular information system was formed, in which tested compounds were described by means of condition attributes, characterizing the structure (substructure parameters and molecular descriptors) and their surface properties, and a decision attribute, classifying compounds with respect to values of MIC. DRSA allows to induce decision rules from data describing the compounds in terms of condition and decision attributes, and to rank condition attributes with respect to relevance using a Bayesian confirmation measure. Decision rules present the most important relationships between structure and surface properties of the compounds on one hand, and their antibacterial activity on the other hand. They also indicate directions of synthesizing more efficient antibacterial compounds. Moreover, the analysis showed differences in the application of various parameters for Gram-positive and Gram-negative strains, respectively.

Highlights

IntroductionCationic surfactants, including bis-imidazolium chlorides ( called gemini-compounds), are able to lower the surface tension while keeping good antimicrobial activity
Cationic surfactants, including bis-imidazolium chlorides, are able to lower the surface tension while keeping good antimicrobial activity
The aim of the work was to understand the structure–activity relationship (SAR) of 140 3,3 -(α, ω-dioxaalkan)bis(1-alkylimidazolium) chlorides on Staphylococcus aureus (SAU) and Pseudomonas aeruginosa (PAE) strains with different susceptibility to antimicrobial compounds

Summary

Introduction

Cationic surfactants, including bis-imidazolium chlorides ( called gemini-compounds), are able to lower the surface tension while keeping good antimicrobial activity. This activity is a result of the interaction of the cationic surfactant with the cell membrane of the microorganism, which leads to the disintegration of membrane structure, the degradation of proteins and nucleic acids, and cell death. The type of interactions and the mechanism of antimicrobial effect depend largely on the surfactant concentration, pH, temperature, type of microorganism, or concentration of other ions. Quaternary ammonium salts (containing quaternary nitrogen in its molecule) are active against Gram-positive bacteria. Gram-negative bacteria are less susceptible to those salts, which results in a tendency to acquire resistance to this group of compounds. The high affinity of the quaternary salts to the biological membranes results in an effective antifungal activity, and ability to inhibit the growth of yeast by inhibiting H+-ATPase [1,2,3]

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Conclusion