Beyond paraquats: Dialkyl 3,3′- and 3,4′-bipyridinium amphiphiles as antibacterial agents

The antimicrobial activity of mono-, bis-, tris-, and tetracationic amphiphiles derived from simple polyamine platforms

“…MIC variation mostly hinged on the length of alkyl chain, where the dodecyl chain was generally found to be optimal, in line with our previous observations. [13][14][15][16] To our surprise, however, the number of cations or basic nitrogens present in the amphiphile was not a key determinant of bioactivity. This was exemplified in the comparison of the X = CH 2 compounds, in both the n,5,n series (1-4) as well as 12,7,12 (20), to the corresponding structures bearing the N-CH 3 group (5, 7-9, 21) or quaternary ammonium groups (10, 12-13, 22, etc.…”

“…We have developed quaternary ammonium amphiphiles based on an all-carbon aromatic core (A), 13 an inexpensive TMEDA core (B), 14 as well as bis-pyridinium structures of both 4,4 0 (C) 15 and other geometries (D), 16 as illustrated in Figure 1. Encouraged by both the precedent of the Falkinham/Gandour polyanionic compounds, as well as the knowledge that bacterial membranes display a significantly anionic surface, we decided to investigate the effect of additional cationic moieties on bioactivity.…”

Biofilm‐Eradicating Properties of Quaternary Ammonium Amphiphiles: Simple Mimics of Antimicrobial Peptides

“…[31,32] As PQs are bis-cationic compounds with delocalized charges, we hypothesized that these compounds would also be potent anti-biofilm agents. Indeed, compound 8, the lead antimicrobial PQ, is one of the most potent compounds to date, with MBEC values of 50 mm against both bacteria evaluated in this study.…”

Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles

“…[10,11] Still others have focused on the designo f" soft" amphiphiles, which incorporateh ydrolyzable bondst hat may decrease toxicity due to their ability to be readily metabolized. [12][13][14] Such QACs typicallyd isplay equipotent activity to their non-hydrolyzable counterparts, while degradinga fter af ew hours to af ew days.O ur laboratories have likewise endeavored to advance our QACc apacities, investigating av ariety of bis-and multiQAC structures; [15][16][17][18][19][20] ar eview of our efforts has recently been reported. [21] Common themes have emerged-optimal alkyl chain lengths are generally~12 carbons, and the incorporation of at least two ammonium cations generally leads to an increase in antimicrobiala ctivity,a s well as significant biofilm eradication capability.MultiQACs also show the promise to address bacterial resistance;whereas bacteria bearing genes for key efflux pumps show increased tolerance toward many commerciallya vailable QACs, resistantb acteria are seemingly thwarted in mostc ases by multicationic systems.…”