Synthesis, Characterization, and Biological Evaluation of Novel 2-{N-Phenyl-N-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]amino}benzenesulfonamide Derivatives

A novel series of 2-(N-phenyl-N-{[1-(R-phenyl)-1H-1,2,3-triazol-4-yl]methyl}amino)benzenesulfonamide derivatives was synthesized via the copper(I)-catalyzed azide–alkyne cycloaddition reaction of substituted alkynes with various aromatic azides. The structures of the synthesized compounds were confirmed by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The antioxidant potential of the products was evaluated using DPPH and HRS assays. The highest activity in both antioxidant assays were demonstrated by the derivatives with R = 4-OH, 4-OMe, and 4-Me. These three compounds also exhibited impressive activities in the antimicrobial assay against Gram-positive (B. subtilis and S. aureus) and Gram-negative (E. coli and S. typhi) bacteria and A. niger and C. albicans fungi. The synthesized compounds were evaluated for their antiproliferative activity using the MTT assay against MCF-7 and PC-3 cell lines. In this assay, the strongest anticancer effect, comparable with that of the standard drug Doxorubicin, was demonstrated by the derivatives with R = 4-CN, 4-Me, and 4-CF3. The former two derivatives also showed the highest VEGFR2 binding affinities (–9.1 and –9.0 kcal/mol, respectively) in the molecular docking study, which provides a possible mechanistic rationale for their observed in vitro antiproliferative activity against MCF-7 and PC-3 cell lines.