Design and synthesis of new bis(α-aminophosphonates) via ultrasound-driven nano-BF3·SiO2 catalysis targeting α-amylase inhibition: In silico ADME and molecular docking study

Abstract

A green and efficient technique for synthesizing α-aminophosphonates (Alpha Aps) 7a–j has been developed through the Kabachnik–Fields (K-F) reaction, catalyzed by nano-BF₃·SiO₂ under solvent-free ultrasonication in good yields (94–98%). Target compounds were developed and prescreened using in silico ADME analysis and molecular docking to establish their drug-like characteristics and potential as α-amylase inhibitors. In vitro α-amylase inhibition experiments were used to determine the biological activity of the produced compounds, which were further characterized structurally using spectroscopy. Compounds 7h (2H-1,3-anthracenyl, IC₅₀ = 86.9 ± 0.4 μg/mL), 7f (naphthalenyl, IC₅₀ = 89.5 ± 0.4 μg/mL), and 7e (1H-indol-5-yl, IC₅₀ = 91.4 ± 0.2 μg/mL) outperformed the reference medication acarbose (IC₅₀ = 92.8 ± 0.6 μg). Compounds 7c and 7i showed inhibition comparable to acarbose, while 7a, 7b, 7d, 7 g, and 7j demonstrated moderate activity (IC₅₀: 105.0–132.7 μg/mL). These findings emphasize the potential of α-aminophosphonate derivatives as next-generation α-amylase inhibitors. They also provide crucial structural insights for future diabetic medication design.