Multicationic Quaternary Ammonium Compounds: A Framework for Combating Bacterial Resistance

Abstract

During previous stages of research, high biocidal activity toward microorganism archival strains has been used as the main indicator in the development of new antiseptic formulations. Although this factor remains one of the most important characteristics of biocide efficiency, the scale of antimicrobial resistance spread causes serious concern. Therefore, focus shifts toward the development of formulations with a stable effect even in the case of prolonged contact with pathogens. Here, we introduce an original isocyanuric acid alkylation method with the use of available alkyl dichlorides, which opened access to a wide panel of multi-QACs with alkyl chains of various lengths between the nitrogen atoms of triazine and pyridine cycles. We used a complex approach for the resulting series of 17 compounds, including their antibiofilm properties, bacterial tolerance development, and antimicrobial activity toward multiresistant pathogenic strains. As a result of these efforts, available compounds have shown higher levels of antibacterial activity against ESKAPE pathogens than widely used commercial QACs. Hit compounds possessed high activity toward clinical bacterial strains and have also demonstrated a long-term biocidal effect without significant development of microorganism tolerance. The overall results indicated a high level of antibacterial activity and the broad application prospects of multi-QACs based on isocyanuric acid against multiresistant bacterial strains.

Highly diastereoselective synthesis of piperidine-2-one-substituted pyridinium salts from pyridinium ylides, aldehydes, Michael acceptors and ammonium acetate

“…These reagents were also obtained by the Knoevenagel condensation between aromatic aldehydes and methyl 2-cyanoacetate. A series of multicomponent reactions under the same conditions with these Michael acceptors resulted in the formation of 1-(5-cyano-5-(alkoxycarbonyl)-2-oxo-4,6-diphenylpiperidin-3-yl)pyridin-1-ium halogenides 5 with four stereogenic centers (Table 1, entries [10][11][12][13][14]. The new multicomponent reaction allows to obtain pyridinium salts of piperidin-2-ones 4, 5 in moderate to high yields in one step from inexpensive and available starting materials via the domino process with the formation of new two C-C and two C-N bonds.…”

“…Pyridinium salts and quaternary ammonium compounds are known to inhibit bacterial and fungal growth (Fig. 1) [7][8][9][10][11][12]. Therefore, obtaining of new pyridinium salts is an urgent task, since the resistance of microorganisms to known drugs increases every year [13].…”

Multiheaded Cationic Surfactants with Dedicated Functionalities: Design, Synthetic Strategies, Self-Assembly and Performance

“…Therefore, the Halder research team's efforts to produce dicephalic cationic surfactants with an easily cleavable ester bond in their structure may eventually result in more effective disinfectants and antiseptics for food and body surfaces than conventional single-headed cationic surfactants. Star-shaped surfactants with multiheaded groups are part of another significant subgroup of MHCSs [152][153][154][155]. The multi-cationic homologs of benzalkonium chloride (BAC) are one of the structures that research teams are now working on, and they look the most promising.…”

Pillar[n]arenes in the Fight against Biofilms: Current Developments and Future Perspectives

“…This review provides an overview of the fundamental concepts, innovative strategies, and recent advances in the use of pillar­[ n ]­arenes with a particular emphasis on cationic derivatives − as they have exhibited effective antibacterial potential. This review investigates how pillar­[ n ]­arenes can help to overcome bacterial resistance and biofilm-associated infections and also discusses the challenges and opportunities in designing biocompatible, stable, and effective antibacterial materials.…”