RESUMEN
Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures. Compounds were obtained in two steps and good yields, with straightforward and chromatography-free purifications. Antibacterial activity evaluation of these compounds against a panel of seven bacterial strains, including two MRSA strains as well as opportunistic pathogen A. baumannii, were encouraging, as low micromolar inhibitory activity was observed for multiple structures. Alkyl chain length on the ammonium group was, as expected, a major determinant of bioactivity. In addition, high therapeutic indexes (up to 125-fold) for triphenyl phosphonium-bearing amphiphiles were observed when comparing antimicrobial activity to mammalian cell lysis activity.
Asunto(s)
Antibacterianos , Desinfectantes , Pruebas de Sensibilidad Microbiana , Compuestos Organofosforados , Compuestos de Amonio Cuaternario , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Amonio Cuaternario/síntesis química , Desinfectantes/farmacología , Desinfectantes/química , Desinfectantes/síntesis química , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Tensoactivos/química , Tensoactivos/farmacología , Tensoactivos/síntesis química , Humanos , Acinetobacter baumannii/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
The preparation of single crystals of sparingly soluble polycyclic aromatic compounds in MeCN is facilitated by solubilizing ionic host-guest complexation under otherwise poor solvent conditions. The guest is then crystallized within minutes through controlled guest displacement from the host via competitor equilibria, or over days through direct crystallization of the host-guest complex itself.