Exploring Synthesis, DFT Characterization, and Molecular Docking of β-Naphthol Derivatives: Investigating Dual Enzyme Inhibition and Antimicrobial Potential with ADMET Profiling

Abstract

Objective: This study aims to design, synthesize, and evaluate novel compounds for the inhibition of α-amylase and α-glucosidase enzymes, with potential applications in enzyme inhibition and antimicrobial therapy. A multidisciplinary approach was employed, integrating molecular docking, in vitro inhibitory assays, and Density Functional Theory (DFT) analysis. Methods: A series of compounds were synthesized and characterized using NMR, IR spectroscopy, and mass spectrometry. Structural modifications were made to enhance enzyme inhibition. Molecular docking, in vitro assays, and structure-activity relationship (SAR) analysis were conducted to assess the relationship between structure and inhibitory activity. Results and Discussion: Molecular docking and SAR analysis revealed that a 3-chloro substituted compound exhibited the strongest inhibition of α-amylase, while a 2-bromo substituted compound was identified as the most potent inhibitor of α-glucosidase. These findings were confirmed by in vitro assays. DFT analysis supported the stability and reactivity of the compounds, and ADME profiling indicated favorable pharmacokinetic properties. Conclusions: This study identified two promising enzyme inhibitors, providing insights for the development of novel therapeutic agents targeting enzyme-related diseases.