Synthesis and Molecular Docking Study of Hydrazone Schiff Bases of α-Naphthalene-Containing Alkyl Phenyl Ether Fragment as Potent α-Amylase and α-Glucosidase Inhibitors

Abstract

In this study, new Schiff base derivatives of α-naphthalene acetic acid containing alkyl phenyl ether fragment have been effectively synthesized through multistep reaction process, characterized by ¹H-NMR and ¹³C-NMR spectroscopy. These derivatives have been tested for their in vitro α-amylase and α-glucosidase inhibitory activities. In the series, 8 compounds (2j, 2f, 2e, 2m, 2a, 2b, 2l, and 2c) exhibited promising α-amylase inhibition with IC₅₀ values from 5.38 ± 0.36  to 14.59 ± 0.64 µg/mL. Similarly, in the case of α-glucosidase inhibitory activity, 10 derivatives (2e, 2f, 2j, 2m, 2b, 2c, 2i, 2d, 2a, and 2l) exhibited excellent activity having IC₅₀ values from 6.96 ± 0.39 to 16.27 ± 0.31 µg/mL, wheras the remaining derivatives exhibited good-to-least antidiabetic potential. The ADME properties were calculated for all Schiff base derivatives using Swiss-ADME web tool. Furthermore, the docking studies identified the binding modes of the compounds.