Benzothiazole based sulfonamide scaffolds as active inhibitors of alpha-Amylase and alpha-glucosidase; synthesis, structure confirmation, In Silico molecular docking and ADME analysis

Abstract

In the current research study, benzothiazole based sulfonamide scaffolds were designed and synthesized having promising efficacy as dual inhibitors of alpha-Amylase & alpha-Glucosidase with a purpose to cure one of the chronic diseases, Diabetes Mellitus. Synthetic confirmation of all the derivatives was accomplished through different spectroscopic techniques, 13C NMR, 1H NMR and HREI-MS. For the evaluation of drug potency of the newly synthesized ligands, biological activity was conducted using the standard drug acarbose (IC50 = 5.40 ± 0.30 µM for α-amylase and 5.70 ± 0.50 µM for α-glucosidase). A wide span of inhibitory potentials were shown by the analogs of current series covering a range of IC50 = 20.70 ± 0.20 µM and 2.10 ± 0.70 µM for α-amylase and 21.40 ± 0.20 µM and 2.40 ± 0.10 µM for α-glucosidase. Potency of the analogs is mainly dependent on the attached substituent moieties, their nature, number and position on the phenyl ring. Based on these protocols, analog-4 with an IC50 = 2.10 ± 0.70 µM for α-amylase and 2.40 ± 0.10 µM for α-glucosidase was found to be the top ranking scaffold with excellent inhibition against the target enzymes in the series. In analog-4, the trifluoromethyl moiety at the para position of the ring, capable to interact through hydrogen bond with active site of the enzyme, is the contributing factor to the efficacy of the analog. Binding insight of the protein-ligand interaction of all the potent analogs was gained through molecular docking study. Furthermore, the drug likeness attributes of the potent derivatives were explored through ADME analysis.