A facile synthesis of a new series of 1,2,3-triazolyl nucleosides via one-pot click reaction is described. Acetylenic nicotinonitriles synthesized previously by alkylation of 4,6-diaryl-2-oxonicotinonitriles with propargyl bromide were involved in cycloaddition with 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl azide in the presence of copper(I) to afford 1,2,3-triazole derivatives which were deprotected by treatment with aqueous triethylamine. The obtained 1,2,3-triazole nucleosides showed significant antimicrobial activities against some Gram-positive and Gram-negative bacteria and fungi