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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases
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[Thrombin inhibitors which display antibacterial activity].

A A Poiarkov, N A Timoshok, N Ia Spivak

    Ukrains'Kyi Biokhimichnyi Zhurnal (1999 )
    |August 6, 2010
    PubMed
    Summary

    Novel synthetic thrombin inhibitors show promising antibacterial activity against Staphylococcus aureus and Bacillus subtilis. These compounds, similar to Nalpha-lauroyl-L-arginine ethyl ester (LAE), offer potential as new antimicrobial agents.

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    A Platform of Anti-biofilm Assays Suited to the Exploration of Natural Compound Libraries

    Published on: December 27, 2016

    Area of Science:

    • Medicinal Chemistry
    • Biochemistry
    • Microbiology

    Background:

    • Thrombin inhibitors are being investigated for novel applications beyond anticoagulation.
    • The antimicrobial properties of synthetic compounds are of increasing interest.
    • Nalpha-lauroyl-L-arginine ethyl ester (LAE) is a known cationic preservative.

    Purpose of the Study:

    • To evaluate the cytotoxicity and antibacterial activity of novel retro-D-peptide thrombin inhibitors.
    • To compare the efficacy of these inhibitors with the known preservative LAE.
    • To explore the potential of these inhibitors as antimicrobial agents.

    Main Methods:

    • Synthesis of novel thrombin inhibitors modified with lauric acid or chromone substituents.
    • Cytotoxicity assessment of the synthesized compounds.
    • Antibacterial activity testing against Staphylococcus aureus and Bacillus subtilis.
    • Comparison of activity and toxicity with Nalpha-lauroyl-L-arginine ethyl ester (LAE).

    Main Results:

    • Laur-D-Arg-D-Phe-OMe exhibited similar cytotoxicity to LAE.
    • Chrom-D-Arg-D-Phe-OMe showed approximately twice the toxicity of its fatty acid analogue.
    • Laur-D-Arg-D-Phe-OMe demonstrated antibacterial activity against Staphylococcus aureus and Bacillus subtilis comparable to LAE.
    • The antibacterial effect is hypothesized to be linked to the inhibition of trypsin-like serine proteinases.

    Conclusions:

    • Novel synthetic thrombin inhibitors possess significant antibacterial properties.
    • These compounds represent a potential new class of antimicrobial agents.
    • The mechanism may involve the inhibition of essential microbial proteinases.