Marine lipids as building blocks for soft quaternary ammonium compounds and their antibacterial activity.
Environmental friendly antibacterial agents have to degrade relatively rapid to non-toxic and inactive products after they have had their desired effect. Environmental friendly quaternary ammonium agents were designed according to Bodor's soft drug approach and evaluated in vitro. Structure-activity relationship (SAR) studies showed that the antibacterial activity of a given soft agent will only be acceptable if its chemical stability is adequate to allow the agent to express its activity for sufficient duration of time. However, the studies also showed that increasing the lipophilicity of a chemically labile antibacterial agent could increase its potency. Two of the lipophilic quaternary ammonium antibacterial agents evaluated had minimum inhibitory concentration (MIC) against Staphylococcus aureus as low as 2 microg/ml and estimated degradation half-life less than 4 to 6 days at room temperature. Decreased MIC could only be obtained by increasing the degradation half-life of the agents.
Loftsson
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T
Faculty of Pharmacy, University of Iceland, Reykjavik, Iceland. thorstlo@hi.is
Thorsteinsson
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T
Másson
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M
D000279:Administration, Cutaneous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D006207:Half-Life; D007928:Lethal Dose 50; D008055:Lipids / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D008386:Marine Biology; D051379:Mice; D008826:Microbial Sensitivity Tests; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D008055:Lipids; D000644:Quaternary Ammonium Compounds