Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds.
A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C.
Thorsteinsson
Thorsteinn
T
Faculty of Pharmacy, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. thorstlo@hi.is
Másson
Már
M
Kristinsson
Karl G
KG
Hjálmarsdóttir
Martha A
MA
Hilmarsson
Hilmar
H
Loftsson
Thorsteinn
T
D000478:Alkylation; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D002594:Cetylpyridinium / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004355:Drug Stability; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds; D000644:Quaternary Ammonium Compounds; D002594:Cetylpyridinium