Design, Synthesis, Characterization, DFT Calculations, Molecular Docking Study, and Antimicrobial Activity of Hydrazones Bearing Pyrimidine and Sugar Moieties

Sugar hydrazones were synthesized by condensation of pyrimidine-2-thione with aldopentoses, aldohexoses and ketohexose. The structures of the new pyrimidines were determined based on their spectral data and elemental analysis. The geometries of the E and Z isomers of the imino group were optimized at B3LYP/6-311G level of theory. DFT results indicated that E-isomer more stable than its Z-isomer in both gas phase and DMSO. The physicochemical properties of the pyrimidines were evaluated using Molsoft tools. The antimicrobial activity of the newly synthesized compounds was evaluated, and they showed good activity. Pyrimidine-hydrazone of D-mannose moiety showed the highest activity against Escherichia coli strain with MIC value 8 mu g/mL. Additionally, molecular docking studies were performed on enoyl reductase from Escherichia coli active sites. The docking score of the ligands ranged between -6.8932 to -8.1090 kcal/mol. Moreover, molecular interaction studies revealed that enoyl reductase had strong hydrogen bonding interactions with pyrimidine ligands. Global chemical descriptors of pyrimidines were calculated to predict their reactivity and correlated with the docking score data.