Synthesis, molecular docking study, molecular dynamics simulation and ADMET prediction of new Sulfa drugs having CA II Inhibitory effect and antidiabetic activity

In this study, new Schiff base (S2M-S2) derived from FDA-approved Sulfa drugs and its Cu (II), Pd (II) complexes were synthesized and their structures were characterized by 1H NMR, 13C NMR, FT-IR and LC-MS analysis methods. In the second stage, CA II Inhibitory effect and antidiabetic activity of the synthesized compounds were investigated. According to studies on enzymes, synthesized compounds showed inhibitory effects on CA II and alpha-glycosidase enzymes. In the course of in vitro investigations, inhibitory effect against hCAII was recorded for S2M-S2 ligand and its Cu (II), Pd (II) complexes with IC50 = 72 mu M, 1.66 mu M and 27 mu M, respectively. While the ligand showed no inhibitory effect on alpha-glycosidase, both copper and palladium metal complexes showed superior activity with IC50 values of 1.28 mu M and 2.5 mu M, respectively. Notably, these values exceeded the inhibitory activity of the standard molecule acarbose (79.63 mu M). The molecules were optimized by DFT/B3LYP functionality and using the 6-311G ++ (d, p) basis set. Molecular docking studies were performed to evaluate the binding interactions between the compounds and the enzymes. When in vitro studies and molecular docking studies are considered together, copper and palladium complexes have promising inhibitory potential compared to the S2M-S2 ligand. In addition, molecular docking and molecular dynamics studies were carried out to investigate alpha-glucosidase enzyme and CA II enzyme binding properties. Subsequently, ADMET properties were investigated to test the drug properties.