Synthesis, characterization, and biocomputational assessment of the novel 3-hydroxy-4-(phenyl(pyridin-2-ylamino) methyl)-2-naphthoic acid derivatives as potential dual inhibitors of α-glucosidase and α-amylase enzymes

Abstract

One-pot synthesis of 3-hydroxy-4-(phenyl(pyridin-2-ylamino) methyl)-2-naphthoic acid derivatives were synthesized by using 3-hydroxy-2-naphthoic acid, aromatic aldehyde, and pyridin-2-amine by refluxing at 140 °C and these derivatives were screened for biological activity as well as computational studies, in that majority of the compounds showed positive results. All synthesized molecules were characterized by analytical technics like 1H NMR and FT-IR. As compared to the control, acarbose (IC50: 0.30 ± 0.08 mg/mL for α-amylase and 0.10 ± 0.06 for α-glucosidase), the compound DMBA (7,12-Dimethylbenz[a]anthracene) nearly inhibited α-glucosidase (IC50: 0.35 ± 0.34 mg/mL) and α-amylase (0.11 ± 0.17 mg/ml) during in vitro inhibition. The DMBA molecule exhibits a good binding affinity (−9.8 kcal/mol for α-glucosidase and −6.6 kcal/mol for α-amylase) compared to that of acarbose (−8.6 kcal/mol and −7.8 kcal/mol, respectively), according to molecular docking studies. The stability of the DMBA molecule was demonstrated by molecular dynamics simulations and estimations of the binding free energy over the course of the simulation session (100 ns). In this context, we report DMBA as a potential dual inhibitor of both α-glucosidase and α-amylase enzymes.

Keywords

• 3-Hydroxy-2-naphthoic acid
• Pyridin-2-amine
• α-Glucosidase
• α-Amylase
• DMBA
• Molecular dynamics simulation