RESUMO
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.
Assuntos
Bactérias/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Compostos de Sulfônio/farmacologia , Tensoativos/farmacologia , Tiofenos/farmacologia , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , Tensoativos/síntese química , Tensoativos/química , Tiofenos/síntese química , Tiofenos/químicaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Tensoativos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Anti-Infecciosos Locais/síntese química , Anti-Infecciosos Locais/química , Desenvolvimento de Medicamentos , Testes de Sensibilidade Microbiana , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Tensoativos/síntese química , Tensoativos/químicaRESUMO
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.