Long-chained quaternary ammonium compounds (QACs) serve as amphiphiles, providing a number of interesting physical properties including the ability to disrupt bacterial cell membranes resulting in lysis.  We have demonstrated that two natural products, quinine and nicotine, can serve as the platform for QAC construction, and that alkylation of these results in structures with significant levels of antibacterial activity. Twenty-eight such mono- and bisQACs were prepared in high yield and evaluated for antimicrobial activity, which was generally in the low micromolar range. We have corroborated previous observations that monoQACs are susceptible to MRSA resistance, observed as an increased MIC in MRSA compared to non-resistant <i>S. aureus</i>. MRSA resistance was not uniformly observed; for select bisQACs (longer chained bisQACs derived from quinine) no resistance at all to MRSA was observed.  In fact, MIC values for two compounds averaged ~2 mM against 6 bacteria tested, demonstrating that natural product derivatives show promise as effective antimicrobials.

Natural product-derived quaternary ammonium compounds with potent antibacterial activity

251st National Meeting (2016)

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