N3-oxoacyl derivatives of L-2,3-diaminopropanoic acid and their peptides; novel inhibitors of glucosamine-6-phosphate synthase.
Novel inhibitors 1-4 of glucosamine-6-phosphate synthase from Candida albicans have been designed based on acylation of the N3 amino group of L-2,3-diaminopropanoic acid with the corresponding ketoacids. These inhibitors have been shown to alkylate the fungal enzyme in a time-dependent manner. Compound 3 containing trans-beta-benzoyl acrylic acid as an acyl residue was found to be the most potent inhibitor in the series. Dipeptides composed of the active inhibitors and norvaline demonstrated potent antifungal activity against selected strains of Candida spp. and Saccharomyces cerevisiae. Their activity was reversed upon addition of N-acetylglucosamine to the medium.
Andruszkiewicz
R
R
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Jedrzejczak
R
R
Zieniawa
T
T
Wojciechowski
M
M
Borowski
E
E
D000478:Alkylation; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005636:Fructosephosphates / Q000378:metabolism; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D008958:Models, Molecular; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D000935:Antifungal Agents; D004151:Dipeptides; D004791:Enzyme Inhibitors; D005636:Fructosephosphates; D015091:beta-Alanine; C011757:2,3-diaminopropionic acid; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)