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

<b>Background:</b> To discover novel lead molecules against diabetes, Alzheimer's disease and oxidative stress, a library of arylated pyrazole-fused pyran derivatives, <b>1-20</b>, were synthesized in a one-pot reaction. <b>Materials &amp; methods:</b>¹H-NMR spectroscopic and electron ionization mass spectrometry techniques were used to characterize the synthetic hybrid molecules <b>1-20</b>. Analogs were screened against four indispensable therapeutic targets, including <i>α</i>-amylase, <i>α</i>-glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes. <b>Results:</b> Except for derivatives <b>17</b> and <b>18</b>, 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 <i>α</i>-amylase and acetylcholinesterase enzymes, as well as a non-competitive mode of inhibition for <i>α</i>-glucosidase and butyrylcholinesterase enzymes. In addition, molecular docking studies identified crucial binding interactions of ligands with the enzyme's active site. <b>Conclusion:</b> These molecules may serve as a potential drug candidate to cure diabetes, Alzheimer's disease and oxidative stress in the future.