[Thrombin inhibitors which display antibacterial activity].
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 Nalpha-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.
Poiarkov
A A
AA
Timoshok
N A
NA
Spivak
N Ia
NIa
Poiarkova
S A
SA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001407:Bacillus / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; C031371:N(alpha)-lauroylarginine ethyl ester; D001120:Arginine; D013917:Thrombin