Synthesis, characterization, and hypoglycemic efficacy of nitro and amino acridines and 4-phenylquinoline on starch hydrolyzing compounds: an in silico and in vitro study

Abstract

α-Amylase and α-Glucosidase are important therapeutic targets for type II diabetes. The present focus of our study is to elucidate the hypoglycemic activity of novel compounds through in vitro and in silico studies. Here, we synthesized the nitro acridines (3a–3c), amino acridines (4a–4c), and nitro phenylquinoline (3d) and amino phenylquinoline (4d) using a multi-step reaction protocol in good yields. All the above derivatives were screened for molecular docking, α-Amylase and α-Glucosidase inhibitory activities utilizing acarbose as standard drug. In silico studies were performed to explore the binding ability of compounds with the active site of α-Amylase and α-Glucosidase enzymes. The in vitro antihyperglycemic report of 3c exhibits the maximum inhibitory activity with IC₅₀ values of 200.61 ± 9.71 μmol/mL and 197.76 ± 8.22 μmol/mL against α-Amylase and α-Glucosidase, respectively. Similarly, the compound 3a exhibits IC₅₀ values of 243.78 ± 13.25 μmol/mL and 296.57 ± 10.66 μmol/mL, and 4c exhibits IC₅₀ values of 304.28 ± 3.51 μmol/mL and 278.86 ± 3.24 μmol/mL with a significant p < 0.05 in both enzyme inhibitions. In addition, the presence of diverse functional moieties in synthesized compounds may provide a strong inhibitory action against the abovementioned enzymes compared with standard acarbose inhibition (IC₅₀, 58.74 ± 3.68 μmol/mL and 49.39 ± 4.94 μmol/mL). Also, the docking studies provided an excellent support for our in vitro studies. The outcome of these studies recommends that the tested compounds might be treated as potential inhibitors for the starch hydrolyzing enzymes in type II diabetes.