Ester- and amide-containing multiQACs: Exploring multicationic soft antimicrobial agents. Issue 10 (15th May 2017)

• Record Type: Journal Article
• Authors: Allen, Ryan A.; Jennings, Megan C.; Mitchell, Myles A.; Al-Khalifa, Saleh E.; Wuest, William M.; Minbiole, Kevin P.C.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 10(2017)
• Page Start: 2107
• Page End: 2112
• Publication Date: 2017-05-15
• Subjects: Antiseptics -- Methicillin-resistant Staphylococcus aureus (MRSA) -- Quaternary ammonium compounds -- Soft antimicrobials; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.077
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 ∼1 μM. 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.