Synthesis, spectroscopic characterizations, enzyme inhibition, molecular docking study and DFT calculations of new Schiff bases of sulfa drugs

Abstract

New Schiff bases were synthesized (Z)-4-((4-(diethylamino)benzylidene)amino)-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide (L1) and (Z)-4-((4-(dimethylamino)benzylidene) amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide (L2) derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehyde. The synthesized compounds were characterized by FT-IR, 1H-13C NMR, LC-MS. We evaluated the effects of compounds on eight enzyme activities by spectrophotometric assays at final concentrations of 0.5–5 μg. L1 acted as an inhibitor on cholesterol esterase, tyrosinase and α-amylase activities with IC50 values 38, 38 and 173 μM. Tyrosinase, α-glucosidase, cholesterol esterase, and α-amylase enzymes were inhibited by L2 with IC50 values 24, 46, 63, and 231 μM. To comprehend the binding interactions between the inhibitors and enzymes with low IC50 values, molecular docking studies of compounds were performed for cholesterol esterase and tyrosinase. Finally, molecular docking was performed to determine the probable binding mode of the designed compounds into the active site of enzymes. DFT calculations were carried out at the B3LYP levels of theory with 6-311G ++ (d, p) basis set for compounds.