Biological Activities, DFT and Molecular Docking Studies of Novel Schiff Bases Derived from Sulfamethoxypyridazine

Abstract The present study reported the synthesis and biological activities of sulfamethoxypyridazine (SMPR) Schiff bases (SBs) with different aromatic aldehydes. The antimicrobial potential of SBs against various pathogenic strains ( S. epidermidis , E. coli , S. agalactiae, S. aureus , S. typhi, K. pneumoniae , C. albicans , and C. tropicalis ) was explored by disc diffusion method. The antidiabetic potential was monitored by inhibition of α ‐amylase, α ‐glucosidase, and anti‐inflammatory activity was studied by protein denaturation assay. The binding of protein with SBs was determined by MOE docking. The synthesized SBs reveal significant antimicrobial potential against all strains ( p values<0.0001) better than the parent drug SMPR but less than amoxicillin. The synthesized SBs exhibited reasonable inhibition potential against α ‐glucosidase, α ‐amylase, and anti‐inflammatory activity. The derivative 10 a depicted antioxidant (IC 50 value 12.18 μ g/mL) and anti‐inflammatory (IC 50 value 49.37 μ g/mL) even better than standard ascorbic acid and diclofenac sodium (IC 50 values 49.92 and 123.81 μ g/mL), respectively. Molecular docking results revealed that synthesized SBs have good binding affinities towards different receptor proteins and results support our experimental results. The electronic properties have been calculated using density function theory (DFT) to determine the chemical reactivity of studied compounds. The low energy gap between Frontier Molecular Orbitals (FMOs) revealed the significant chemical reactivity of compounds 8 a and 10 a , among other compounds.