ABSTRACT
N-substituted isomeric hydrazones of uridyl aldehyde have been synthesized. The occurrence of the dominant E isomers with respect to the azomethine group was confirmed by means of NMR spectroscopy. Synthesized hydrazones feature an acetonide moiety as a protection of two hydroxyl groups on the ribose part. The attempt to remove the protecting group resulted in an azo-hydrazone tautomeric mixture. The described compounds may be valuable chiral ligands for metal chelation. Assessment of manganese(II) ion affinity to one selected hydrazone was performed.
Subject(s)
Hydrazones/chemistry , Aldehydes/chemistry , Chelating Agents/chemistry , Hydrazones/chemical synthesis , Hydrazones/metabolism , Isomerism , Ligands , Magnetic Resonance Spectroscopy , Manganese/metabolism , Uridine/chemistryABSTRACT
This study described the synthesis and in vitro evaluation of eight new derivatives of uridine as antifungal agents and inhibitors of chitin synthase. Dimeric uridinyl derivatives synthesized by us did not exhibit significant activity. One of the studied monomeric derivative, 5'-(N-succinyl)-5'-amino-5'-deoxyuridine methyl ester (compound 7) showed activities against several fungal strains (MIC range 0.06-1.00 mg/mL) and inhibited chitin synthase from Saccharomyces cerevisiae (IC50=0.8mM). Moreover compound 7 exhibited synergistic interaction with caspofungin against Candida albicans (FIC index=0.28).
Subject(s)
Antifungal Agents/chemistry , Chitin Synthase/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Uridine/analogs & derivatives , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Aspergillus niger/drug effects , Candida albicans/drug effects , Chitin Synthase/metabolism , Dimerization , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Microbial Sensitivity Tests , Rhizopus/drug effects , Saccharomyces cerevisiae/enzymology , Uridine/chemical synthesis , Uridine/pharmacologyABSTRACT
New 5'-glycyl derivatives of uridine containing fragments of varying lipophilicity were synthesized as analogues of natural peptidyl antibiotics. One of the studied compounds, 5'-O-(N-succinylglycyl)-2',3'-O-isopropylideneuridine (A4), showed moderate inhibition against 1,4-ß-galactosyltransferase. However, additional studies showed that the observed inhibitory effect was due to binding to bovine serum albumin, which was used in assays as a stabilizer.
Subject(s)
Enzyme Inhibitors/chemistry , Galactosyltransferases/antagonists & inhibitors , Uridine/analogs & derivatives , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , Uridine/chemical synthesis , Uridine/pharmacologyABSTRACT
New derivatives of uridine which contain a b-ketoenol motif were synthesized, characterized and biologically tested. Synthesized compounds 1-4 showed no activity against bovine milk ß-1,4-galactosyltransferase I at concentrations up to 2.0 mM and were not active against Candida albicans and Aspergilus fumigatus up to the maximum tested concentration of 1,000 µg/mL.
