Ultrasound mediated nano ZnO catalyzed synthesis of new α-aminophosphonates as potential anti-diabetic agents; an in silico ADMET, molecular docking study, α-amylase and α-glucosidase inhibitory activity

Abstract

A more efficient and ecologically friendly method has been devised for the preparation of α-amino phosphonates by Kabachnik-Fields (K-F) reaction in a solvent-free environment using an ultrasonication technique catalyzed by nano ZnO. Primarily, an in silico ADMET and molecular docking analysis was carried out on each molecule prior to synthesis to get insight into drug-likeliness behavior and their capacity to inhibit α-amylase and α-glucosidase. The structure of the newly synthesized compounds was confirmed using spectroscopic analysis, and each one’s in vitro inhibitory action against α-amylase and α-glucosidase was evaluated. The compounds diethyl (4-(4-oxo-4H-chromen-2-yl)phenylamino)(4-hydroxy-3-nitrophenyl)methylphosphonate (7e) and diethyl (4-(4-oxo-4H-chromen-2-yl)phenylamino)(benzo[d][1,3]dioxol-6-yl)methylphosphonate (7h) exhibited the highest inhibitory activity against α-amylase in comparison to the reference substance acarbose. The compounds diethyl (4-(4-oxo-4H-chromen-2-yl)phenylamino)(4-fluorophenyl)methylphosphonate (7d), diethyl (4-(4-oxo-4H-chromen-2-yl)phenylamino)(3-(trifluoromethyl)phenyl)methylphosphonate (7 g) and diethyl (4-(4-oxo-4H-chromen-2-yl)phenylamino)(benzo[d][1,3]dioxol-6-yl)methylphosphonate (7h) have shown the highest inhibitory activity against α-glucosidase than the reference drug, Acarbose. The remaining compounds have shown equipotent to good inhibitory activity against both the tested enzymes.

Graphical Abstract

Keywords:

• α-aminophosphonates
• α-amylase
• α-glucosidase
• Kabachnik-Fields reaction
• molecular docking
• ultrasonication

Acknowledgements

The authors thank Dr. S. Someswar Rao, Department of Genetics of Osmania University for his assistance with bioactivity investigations and Dr. C. Naga Raju, Department of Chemistry, S. V. University for his unwavering support throughout the completion of this work.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.