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Journal archive > 2010 > N 1 January-February

THROMBIN INHIBITORS WHICH DISPLAY ANTIBACTERIAL ACTIVITY

A. A. Poyarkov1, N. A. Timoshok2, M.Ya.Spivak2, S. A. Poyarkova1

1Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kyiv;
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2Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Kyiv;
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The investigation of cytotoxicity and antibacterial activity of the novel thrombin inhibitors containing retro-D-sequences -D-Arg-D-Phe – modified by D-arginine amino group by the residues of lauric acid or chromone-contained substituent, in comparison with known cationic preservative N?-lauroyl-L-arginine ethyl ester (LAE) have been carried out. It has been shown that compound Laur-D-Arg-D-Phe-OMe has a similar cytotoxicity with LAE, and Chrom-D-Arg-D-Phe-OMe has almost twice higher toxicity than it fatty moiety contained analogues. Antibacterial activity of Laur-D-Arg-D-Phe-OMe against Staphylococcus aureus and Bacillus subtilis is close in action to LAE. It is assumed that ability of thrombin inhibitors to suppress the growth of some microorganisms can be explained by their ability to suppress activity of trypsin-like serine proteinases, which participate in the infection process of Staphylococcus aureus and influence on Bacillus subtilis sporulation.
These findings open new prospects for exploring­ efficient antimicrobial agents among synthetic low-molecular trypsin-like serine proteinase inhibitors.

Key words: thrombin inhibitors, antibacterial activity, cytotoxicity, retro-D-peptide, N?-lauroyl-L-arginine ethyl ester (LAE).

The original article in Russian is available for download in PDF format.

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