In silico ADMET, molecular docking study, and nano Sb2O3-catalyzed microwave-mediated synthesis of new α-aminophosphonates as potential anti-diabetic agents

Abstract

An efficient and greener method is developed for the synthesis of α-aminophosphonates via Kabachnik–Fields reaction in solvent free condition using microwave irradiation technique. For all of the compounds, an in silico ADMET and molecular docking study was conducted to get insight on the drug likeliness behavior as well as their ability to block the enzyme α-amylase. The compounds with significant binding affinity and significant pharmacokinetic characteristics were produced. The newly produced compounds were spectroscopically analyzed to confirm their structure, and in vitro α-amylase inhibitory activity was also tested for all of them. The compounds 8j (half-maximal inhibitory concentration (IC50), 100.5 ± 0.2 μg·mL−1) showed better inhibitory activity than the reference drug, acarbose. The compounds 8d (IC50, 108.6 ± 0.2 μg·mL−1), 8g (IC50, 110.9 ± 0.3 μg·mL−1), 8h (IC50, 115.0 ± 0.1 μg·mL−1), and 8f (IC50, 118.9 ± 0.2 μg·mL−1) have been reported to exhibit significant inhibition toward the target enzyme. All the leftover compounds displayed modest to excellent inhibition through IC50 values in the range from 122.3 ± 0.3 to 154.3 ± 0.6 μg·mL−1 while comparing with the reference drug, Acarbose (IC50, 103.2 ± 0.7 μg·mL−1). The results disclosed that the majority of these compounds exhibit significant α-amylase inhibitory activity.

Keywords

• α-aminophosphonates
• kabachnik–fields reaction
• microwave irradiation
• molecular docking
• α-amylase