Benzimidazolium salts prevent and disrupt methicillin-resistant Staphylococcus aureus biofilms

Abstract

Emergence of resistant bacteria encourages us to develop new antibiotics and strategies to compensate for the different mechanisms of resistance they acquire. One of the defense mechanisms of resistant bacteria is the formation of biofilms. Herein we show that benzimidazolium salts with various flexible or rigid side chains act as strong antibiotic and antibiofilm agents. We show that their antibiofilm activity is due to their capacity to destroy the biofilm matrix and the bacterial cellular membranes. These compounds are able to avoid the formation of biofilms and disperse mature biofilms showing a universal use in the treatment of biofilm-associated infections.rsc.li/rsc-advances 9420 | RSC Adv., 2020, 10, 9420-9430This journal is Scheme 1 Synthesis of second and third generation analogues.9422 | RSC Adv., 2020, 10, 9420-9430This journal is

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

“…The third series ( 10a – 14d ) was prepared by the reaction of dibromoalkanes with the alkyl-benzimidazoles ( 1a – 1d ). Finally, the fourth series ( 15a – 15c ) was obtained by treating 4,4-dibromobiphenyl with the various benzimidazole precursors ( 1a – 1c ) . The synthesized compounds were characterized by 1 H NMR, 13 C NMR, HRMS, and HPLC purity percentages, and the details of the synthesis and characterization are reported in the Supporting Information.…”

“…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). 44 The first series of analogues 4a−8d was obtained in a twostep reaction starting with the diamine reacted with bromoacetylbromide, yielding the intermediate N,N-alkanedibromoethanamide (3a−3e), followed by substitution with the alkyl-benzimidazole precursors (1a−1d) (Scheme 3). 44 The second series (9a−9d) was prepared by the reaction of individual solutions of 1a−1d with bis(2-bromoethyl)ether.…”

“…44 The first series of analogues 4a−8d was obtained in a twostep reaction starting with the diamine reacted with bromoacetylbromide, yielding the intermediate N,N-alkanedibromoethanamide (3a−3e), followed by substitution with the alkyl-benzimidazole precursors (1a−1d) (Scheme 3). 44 The second series (9a−9d) was prepared by the reaction of individual solutions of 1a−1d with bis(2-bromoethyl)ether. The third series (10a−14d) was prepared by the reaction of dibromoalkanes with the alkyl-benzimidazoles (1a−1d).…”

Synthesis and antimicrobial activity of novel bis-benzimidazolium salts

“…Previously, various organic cationic compounds demonstrated strong antibacterial and antibiofilm properties. [7][8][9] The amphiphilic nature of these compounds (Fig. 1a) is brought by the presence of two benzimidazolium cations substituted with two phenylethynylbenzyl groups.…”

Benzimidazolium Salts Bearing Nitrile Moieties: Synthesis, Enzyme Inhibition Profiling, and Molecular Docking Analysis for Carbonic Anhydrase and Acetylcholinesterase

“…[22][23][24][25][26][27][28] Benzimidazolium salts are derivatives of 1,3-disubstituted benzimidazole and possess acidic hydrogen in the 2-position. Benzimidazolium salts are gaining attention for their significant pharmacological applications, including anticancer, antibiofilm, antibacterial, antifungal, and enzyme inhibition [29][30][31][32][33][34] Carbonic anhydrase (EC 4.2.1.1, CA) is a ubiquitous class of zinc-containing metalloenzymes found in both prokaryotes and eukaryotes. [35,36] These metalloenzymes efficiently catalyze the reversible essential hydration of carbon dioxide.…”