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Allen RA, Jennings MC, Mitchell MA, Al-Khalifa SE, Wuest WM, Minbiole KP
Ester- and amide-containing multiQACs: Exploring multicationic soft antimicrobial agents
Bioorg Med Chem Lett (2017) 27:2107-2112.
Quaternary ammonium compounds (QACs) are ubiquitous antiseptics whose chemical stability is both an aid to prolonged antibacterial activity and a liability to the environment. Soft antimicrobials, such as QACs designed to decompose in relatively short times, show the promise to kill bacteria effectively but not leave a lasting footprint. We have designed and prepared 40 soft QAC compounds based on both ester and amide linkages, in a systematic study of mono-, bis-, and tris-cationic QAC species. Antimicrobial activity, red blood cell lysis, and chemical stability were assessed. Antiseptic activity was strong against a panel of six bacteria including two MRSA strains, with low micromolar activity seen in many compounds; amide analogs showed superior activity over ester analogs, with one bisQAC displaying average MIC activity of approximately 1muM. For a small subset of highly bioactive compounds, hydrolysis rates in pure water as well as buffers of pH =4, 7, and 10 were tracked by LCMS, and indicated good stability for amides while rapid hydrolysis was observed for all compounds in acidic conditions.
Publication Date: 2017-05-15.
Last updated on Tuesday, June 05, 2018