POLYVALENT PYRIDINIUM- AND QUINOLINIUM-SUBSTITUTED TRIAZOLES AS ANTISEPTICS.

Quaternary ammonium compounds (QACs) composed of N-heterocycles such as cetylpyridinium chloride are common commercial disinfectants. Recently, click-derived 1,2,3-triazolium salts have been shown to display antiseptic properties in a substituent dependent manner. The aim of this study was to prepare both pyridinium-substituted 1,2,3-triazole QACs and quinolinium-substituted 1,2,3-triazole QACs, as well as polyvalent hybrid salts possessing both pyridinium or quinolinium and triazolium subunits, and to evaluate their respective antiseptic properties. Under mild conditions, N-benzylation at either single nitrogen-containing heterocycle subunit could be achieved selectively over N-benzylation at the 1,2,3-triazole subunit. Under forcing conditions, N-benzylation at both single nitrogen-containing heterocycle subunits and 1,2,3-triazole subunits to form a hybrid polyvalent QAC was achievable. When comparing the ability of bis-triazole, para-phenyl bridged bis-triazole and para-biphenyl bridged bis-triazole analogs, the efficiency of preparing polyvalent hybrid triazolium products was distance-dependent with respect to the other heterocycle. Monovalent and polyvalent QACs were evaluated for antiseptic properties against exemplary Gram-positive bacteria (S. epidermidis and B. subtilis), Gram-negative bacteria (E. coli and K. aerogenes), and yeast (C. albicans and S. cerevisiae) using minimum inhibitory concentration assays. Micromolar MIC values were observed for select analogs, with overall charge as well as peripheral substituent identity influencing antiseptic potency. Details regarding the synthesis of target compounds, examination of relative N-benzylation rates and evaluation of antiseptic potency will be presented. This publication was made possible by grants from the National Institute for General Medical Science (NIGMS) (5P20GM103427), a component of the National Institutes of Health (NIH), and its contents are the sole responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. [ABSTRACT FROM AUTHOR]