Efficient one-pot synthesis of arylated pyrazole-fused pyran analogs: as leads to treating diabetes and Alzheimer's disease.

To discover novel lead molecules against diabetes, Alzheimer's disease and oxidative stress, a library of arylated pyrazole-fused pyran derivatives, , were synthesized in a one-pot reaction. H-NMR spectroscopic and electron ionization mass spectrometry techniques were used to characterize the synthetic hybrid molecules . Analogs were screened against four indispensable therapeutic targets, including -amylase, -glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes. Except for derivatives and , all other compounds exhibited varying degrees of inhibitory activities against target enzymes. The kinetic studies revealed that the synthetic molecules followed a competitive-type mode of inhibition for -amylase and acetylcholinesterase enzymes, as well as a non-competitive mode of inhibition for -glucosidase and butyrylcholinesterase enzymes. In addition, molecular docking studies identified crucial binding interactions of ligands with the enzyme's active site. These molecules may serve as a potential drug candidate to cure diabetes, Alzheimer's disease and oxidative stress in the future.