Rational Design of Gram-Specific Antimicrobial Imidazolium Tetramers To Combat MRSA

Abstract

Antimicrobial resistance poses an increasingly serious global health threat. Hence, new antimicrobials with low propensity toward inducing resistance in bacteria are being developed to combat this threat. In this work, a series of imidazolium tetramers have been synthesized by modulating the linkers between imidazoliums or the length of the end groups within the structures of oligomers in order to optimize the activity, selectivity, and biocompatibility of the compounds. These new materials possess high biocompatibility, Gram selectivity, and high efficacy against the selected bacterium as well as clinically isolated methicillin-resistant Staphylococcus aureus species without inducing drug resistance. Therefore, we believe that these compounds can potentially be used to mitigate resistance as highly effective disinfectants in healthcare products or as antimicrobial therapies specifically for Gram-positive bacterial infections.

Gram-selective antibacterial peptide hydrogels

“…[28][29][30] As in the case of common antibiotics, narrow-spectrum AMPs are urgently needed to target specific pathogens without damaging other normal microbes. 31 To date, the hydrophilicity/hydrophobicity and charge properties of peptide molecules have been finetuned to design AMPs that specifically targeted Grampositive 32,33 and Gram-negative [34][35][36] bacteria, respectively.…”

Confronting the Threat: Designing Highly Effective bis-Benzimidazolium Agents to Overcome Biofilm Persistence and Antimicrobial Resistance

“…Experimental protocol from Yuan et al was followed. 43 MRSA ATCC 43300 and E. coli SK039 were repeatedly treated with a gradient of concentration of bis-benzimidazolium salts, BAC, or conventional antibiotics. After each exposition, the MIC was determined and then the sub-MIC (1/2 MIC) bacteria were resuspended and incubated for 18 h at 37 °C, 180 rpm.…”

“…It is worth noting that the synthesis of bis-benzimidazolium salts involved a simple two-step method. The first step involved the synthesis of 1-alkyl-benzimidazoles from the corresponding 1bromoalkanes with benzimidazole (Scheme 1) 43 followed by dimerization of the benzimidazoles with various linkers to obtain the final bis-benzimidazolium salts. The precursors 1a− 1c were synthesized from the corresponding 1-bromoalkanes with benzimidazole, while 1d was synthesized from phenylethynylbenzyl bromide obtained from a Sonogashira coupling between phenylacetylene and 4-iodobenzylmethanol followed by a bromination step (Scheme 2).…”

Imidazolium-Based Heavy-Atom-Free Photosensitizer for Nucleus-Targeted Fluorescence Bioimaging and Photodynamic Therapy

“…Moreover, imidazolium salts have exhibited selective antibacterial activity against Gram-positive bacteria. 37 This selectivity arises from the positive charge of imidazolium salts, which enables electrostatic interactions with the negatively charged bacterial membrane. 38,39 This attribute suggests the potential use of imidazolium-based compounds as antimicrobial agents, offering a novel approach to combating bacterial infections.…”