One-Pot Synthesis of Pyrazole-Containing 1,2,3-Triazoles: In Vitro and In Silico Antibacterial Activity

Abstract Objective: The current study aims to synthesize novel pyrazole-containing 1,2,3-triazole derivatives via a one-pot method and evaluate their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Staphylococcus epidermidis strains. Methods: The target 1,2,3-triazoles were obtained through a one-pot reaction involving 1-methyl-1H-pyrazol-4-amine, triflyl azide (TfN3), and various terminal alkynes via in situ generation of 4-azido-1-methyl-1H-pyrazole. The antibacterial activity of the newly synthesized compounds was assessed using the broth microdilution method. Results and Discussion: The structures of the synthesized compounds were confirmed by 1H, 13C NMR, and mass spectrometry. Compound 4l exhibited potent activity against the tested bacterial strains with MIC values ranging from 3.12 ± 0.41 to 9.7 ± 0.51 µg/mL. Compound 4k also demonstrated good activity against B. subtilis and S. aureus with MIC values of 5.9 ± 0.20 and 7.5 ± 0.56 µg/mL, respectively. These results are comparable to the standard antibiotic dicloxacillin. Conclusions: A new series of pyrazole-containing 1,2,3-triazoles was synthesized and evaluated for in vitro antibacterial activity. Several compounds showed promising efficacy against the tested strains. The most active compounds were subjected to in silico studies. With further structural optimization, these compounds have the potential to be developed as future therapeutic candidates.