Design, synthesis and biological evaluation of furan based α-aminophosphonate derivatives as anti-Alzheimer agent

A series of novel α -aminophosphonates bearing furan motif were designed and were synthesized under solvent-free condition and further evaluated for inhibition activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and antioxidant property. All the synthesized compounds 4(a-h) showed good inhibition against AChE (IC 50 = 0.88–4.46 µM) and BuChE (IC 50 = 2.30–18.59 µM). Compound 4c was found to have maximum inhibitory potential against AChE with IC 50 = 0.884 ± 0.002 µM while IC 50 = 2.297 ± 0.091µM BuChE, suggesting that the synthesized compound are dual-inhibitors. Molecular docking studies suggested that the compound binds to both peripheral anionic site and catalytic anionic site which corroborate with the results obtained in kinetic inhibition suggesting a mixed-type inhibition. Predicted ADME showed good drug-likeness properties. Further, antioxidant activity using DPPH radical was performed; it was observed that all the compounds showed promising antioxidant activity. The highest antioxidant property was exhibited by compound 4c with IC 50 value 30.04 when compared to ascorbic acid. Graphical abstract