Further Investigations into Rigidity‐Activity Relationships in BisQAC Amphiphilic Antiseptics. (11th February 2020)

• Record Type: Journal Article
• Authors: Leitgeb, Austin J.; Feliciano, Javier A.; Sanchez, Hugo A.; Allen, Ryan A.; Morrison, Kelly R.; Sommers, Kyle J.; Carden, Robert G.; Wuest, William M.; Minbiole, Kevin P. C.
• Is Part Of: ChemMedChem. Volume 15:Number 8(2020)
• Page Start: 667
• Page End: 670
• Publication Date: 2020-02-11
• Subjects: antiseptics -- quaternary ammonium compounds -- methicillin-resistant Staphylococcus aureus (MRSA) -- bisQACs; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201900662
• Languages: English
• ISSNs: 1860-7179

Abstract

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. 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).