A series of new uncharged conjugates of adenine, 3,6-dimetyl-, 1,6-dimethyl- and 6-methyluracil with 1,2,4-triazole-3-hydroxamic and 1,2,3-triazole-4-hydroxamic acid moieties were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. It is shown that triazole-hydroxamic acids can reactivate acetylcholinesterase (AChE) inhibited by paraoxon (POX) in vitro, offering reactivation constants comparable to those of pralidoxime (2-PAM). However, in contrast to 2-PAM, triazole-hydroxamic acids demonstrated the ability to reactivate AChE in the brain of rats poisoned with POX.
View Article and Find Full Text PDFWe considered it timely to test the applicability of transferable multipole pseudo-atoms for restoring inner-crystal electronic force density fields. The procedure was carried out on the crystal of 1,3-bis(2-hydroxyethyl)-6-methyluracil, and some derived properties of the scalar potential and vector force fields were compared with those obtained from the experimental multipole model and from the aspherical pseudo-atom model with parameters fitted to the calculated structure factors. The procedure was shown to accurately replicate the general vector-field behavior, the peculiarities of the quantum potentials and the characteristics of the force-field pseudoatoms, such as charge, shape and volume, as well as to reproduce the relative arrangement of atomic and pseudoatomic zero-flux surfaces along internuclear regions.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
July 2023
A series of 1,2,3-triazolyl nucleoside analogues bearing -acetyl-D-glucosamine residue was synthesized by the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of 1-ω-alkynyl derivatives of uracil, 6-methyluracil, thymine and 3,4,6-tri--acetyl-2-deoxy-2-acetamido-β-D-glucopyranosyl azide. Antiviral assays revealed the lead compound which showed both the same activity against the influenza virus A H1N1 (IC=70.7 µM) as the antiviral drug Rimantadine in control (IC=77 µM) and good activity against Coxsackievirus B3 (IC=13.
View Article and Find Full Text PDFA series of new compounds in which uracil and 3,6-dimethyluracil moieties are bridged with different spacers were prepared and evaluated in vitro for the acetyl- and butyrylcholinesterase (AChE and BChE) inhibitory activities. These bisuracils are shown to be very effective inhibitors of AChE, inhibiting the enzyme at nano- and lower molar concentrations with extremely high selectivity for AChE vs. BChE.
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