Efficient synthesis, spectroscopic characterization, DFT analysis, antibacterial activity and docking studies of novel sulfonyl-1,2,3-triazole derivatives

In this work, we employed a practical 1,3-dipolar cycloaddition reaction, followed by O-alkylation using tosyl chloride, to synthesize two novel tosyl-1,2,3-triazole derivatives based on salicylaldehyde with satisfactory yields. The structures of the resulting compounds were thoroughly characterized using NMR, IR, UV, and HRMS techniques. Comparative analysis of 9a-b through IR, UV-Vis, NMR spectra, and surface visualization highlighted the influence of substituent groups on their structural and electronic features. Minor variations in vibrational frequencies, electronic transitions, and chemical shifts demonstrated how modifications in the molecular framework affect their overall behavior. Surface visualization further corroborated these findings, illustrating improved electronic delocalization and intermolecular interactions in compound 9b. These observations not only enhance our understanding of the relationship between structure and properties but also provide valuable insights for potential applications in material science and drug design. Our analysis underscores the advantages of 9b over 9a, particularly in terms of its stability, superior optical properties, and binding affinity. Moreover, the antibacterial efficacy was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacterium Staphylococcus aureus. The results from the bioassays demonstrated that compound 9b inhibited the growth of Staphylococcus aureus at a concentration of 2.34 μmol/mL. Additionally, compounds 9a and 9b showed moderate activity against Escherichia coli, with MIC and MBC values ranging from 2.56 to 7.23 μmol/mL. Compound 9b demonstrates the strongest binding affinity with DHFR, with a docking score of -8.74 kcal/mol, outperforming both compound 9a and ampicillin. In silico studies, including molecular docking, were conducted on the synthesized compounds against STAT3, revealing favorable binding energies of -3.95 kcal/mol for 9a and -4.43 kcal/mol for 9b (Capivasertib showed -4.41 kcal/mol), complemented by pharmacological network analysis. Additionally, molecular dynamics simulations were performed to assess the stability of these compounds within the binding site of the STAT3 protein. These findings position compound 9b as a promising candidate for pharmaceutical applications, particularly in cancer therapy.