Volume 15, Issue 8 p. 667-670
Communication

Further Investigations into Rigidity-Activity Relationships in BisQAC Amphiphilic Antiseptics

Austin J. Leitgeb

Austin J. Leitgeb

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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Javier A. Feliciano

Javier A. Feliciano

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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Hugo A. Sanchez

Hugo A. Sanchez

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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Ryan A. Allen

Ryan A. Allen

Department of Chemistry, Emory University, Atlanta, GA, 30322 USA

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Kelly R. Morrison

Kelly R. Morrison

Department of Chemistry, Emory University, Atlanta, GA, 30322 USA

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Kyle J. Sommers

Kyle J. Sommers

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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Dr. Robert G. Carden

Dr. Robert G. Carden

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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Prof. William M. Wuest

Corresponding Author

Prof. William M. Wuest

Department of Chemistry, Emory University, Atlanta, GA, 30322 USA

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Prof. Kevin P. C. Minbiole

Corresponding Author

Prof. Kevin P. C. Minbiole

Department of Chemistry, Villanova University, Villanova, PA, 19085 USA

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First published: 05 February 2020
Citations: 18

Graphical Abstract

Stay flexible: To further probe the rigidity-activity relationship in quaternary ammonium compounds (QACs), 36 bisQACs were synthesized and tested against a range of both Gram-positive and Gram-negative bacterial strains. A modest, negative correlation between rigidity and activity was observed, and several synthesized compounds displayed low-micromolar activity against both hospital-acquired and community-acquired methicillin-resistant Staphylococcus aureus (MRSA).

Abstract

Thirty-six biscationic quaternary ammonium compounds were efficiently synthesized in one step to examine the effect of molecular geometry of two-carbon linkers on antimicrobial activity. The synthesized compounds showed strong antimicrobial activity against a panel of both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). While the linker geometry showed only a modest correlation with antimicrobial activity, several of the synthesized bisQACs are promising potential antiseptics due to good antimicrobial activity (MIC≤2 μM) and their higher therapeutic indices compared to previously reported QACs.