Antibacterial activity of 5-acylaminothiazole derivatives, synthetic drugs related to beta-lactam antibiotics.
Newly synthesized 5-acylaminothiazolium salts and one 5-acylaminothiazolidine, considering their chemical structure and reactivity, have been proposed as potential inhibitors of bacterial serine DD-peptidases. A moderate antibiotic activity with (5-phenylacetylamino-3-thiazolio)acetate and (5-phenylacetylaminothiazolidin-3-yl)acetic acid was observed on Staphylococcus aureus ATCC 25923. The methyl- and tert-butyl esters of the thiazolium salt have shown lower MIC values. Moreover, when introduced into an exponential growth phase culture of S. aureus, the three active thiazolium salts induced a partial lysis indicating an impairing of the bacterial cell wall biosynthesis. The observed time-dependent binding of the best compound to the PBPs of S. aureus was too slow and occurred at too high concentrations to account for its MIC value. Consequently, the antibiotic activity of the thiazolium salts on the S. aureus cells seems not to be satisfactorily explained by a penicillin-like interaction with the PBPs.
Department of Medicinal Chemistry, Université de Liège, Belgium.
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B
Pirotte
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Delarge
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Coyette
J M
JM
Frere
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; D047090:beta-Lactams