Abstract
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.