Novel 1, 2, 3-triazolic compounds derived from cytosine: Synthesis, spectroscopic characterization, in vitro antimicrobial activity and molecular docking studies

Abstract

The development of novel antimicrobial drugs is crucial due to the increasing problem of antibiotic resistance. A new series of 1,4-disubstituted-1,2,3-triazole derivatives containing a cytosine moiety (3a, 3b, 3c and 3d) were synthesized using 1,3-dipolar cycloaddition in a mixture of ethanol and water under Cu(I)-catalyzed with N-alkyl: 1-(prop-2-ynyl)-4-amino-2-oxopyrimidine 2 as dipolarophiles and azide derivatives (sucre-azoture) as dipoles. The desired products were obtained in good yields by reacting with a catalytic amount of copper (II) sulfate and sodium ascorbate. The structure of these compounds was analyzed and characterized using spectroscopic measurements such as 1H NMR, 13C NMR, and mass spectroscopy. Encouragingly, all cycloaddition molecules exhibited promising activity against various bacterial strains including Staphylococcus aureus and Escherichia coli. The crystal structure modeling of protein 7AZ5 demonstrated strong binding affinities through hydrogen bonds with these molecules. The cycloaddition compounds displayed the highest binding energies in terms of antimicrobial efficacy. This suggests that these substances could serve as an effective model for the development and production of new and potent antimicrobial agents.

Keywords

• Cycloaddition
• Triazoles
• Cytosine
• Antimicrobial activity
• Docking studies