ABSTRACT
Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC. The development of these compounds presents a new avenue for further study of disinfectants to combat the growing threat of bacterial resistance.
Subject(s)
Bacteria/drug effects , Quaternary Ammonium Compounds/pharmacology , Sulfonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Thiophenes/pharmacology , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/metabolism , Humans , Microbial Sensitivity Tests , Molecular Structure , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Structure-Activity Relationship , Sulfonium Compounds/chemical synthesis , Sulfonium Compounds/chemistry , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistry , Thiophenes/chemical synthesis , Thiophenes/chemistryABSTRACT
The prevalence of quaternary ammonium compounds (QACs) as common disinfecting agents for the past century has led bacteria to develop resistance to such compounds. Given the alarming increase in resistant strains, new strategies are required to combat this rise in resistance. Recent efforts to probe and combat bacterial resistance have focused on studies of multiQACs. Relatively unexplored, however, have been changes to the primary atom bearing positive charge in these antiseptics. Here we review the current state of the field of both phosphonium and sulfonium amphiphilic antiseptics, both of which hold promise as novel means to address bacterial resistance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Infective Agents, Local/pharmacology , Bacteria/drug effects , Drug Resistance, Bacterial/drug effects , Quaternary Ammonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Infective Agents, Local/chemical synthesis , Anti-Infective Agents, Local/chemistry , Drug Development , Microbial Sensitivity Tests , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistryABSTRACT
Thirty-six biscationic quaternary ammonium compounds were efficiently synthesized in one step to examine the effect of molecular geometry of two-carbon linkers on antimicrobial activity. The synthesized compounds showed strong antimicrobial activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). While the linker geometry showed only a modest correlation with antimicrobial activity, several of the synthesized bisQACs are promising potential antiseptics due to good antimicrobial activity (MIC≤2â µM) and their higher therapeutic indices compared to previously reported QACs.
