Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3-diaryltriazene-substituted sulfathiazole derivatives.

ABSTRACT

In the present study, a series of eleven novel 1,3-diaryltriazene-substituted sulfathiazole moieties (ST1-11) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α-glycosidase (α-GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), with KI values in the range of 426.84 ± 58.42-708.61 ± 122.67 nM for α-GLY, 450.37 ± 50.35-1,094.34 ± 111.37 nM for hCA I, 504.37 ± 57.22-1,205.36 ± 195.47 nM for hCA II, and 68.28 ± 10.26-193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4-[3-(perfluorophenyl)triaz-1-en-1-yl]-N-(thiazol-2-yl)benzenesulfonamide) showed a highly efficient inhibition profile against hCA I, hCA II, and AChE, with KI values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes.