Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors

An efficient, borax-catalyzed protocol for the synthesis of novel 4-aryl-substituted-4H-pyran derivatives fused to alpha-pyrone ring in a one-pot is described. By this achievement, some novel 4-aryl substituted 4H-pyrans fused to the alpha-pyrone ring as potential acetylcholinesterase inhibitors (AChEIs) with good to excellent yields are obtained from a one-pot three-component reaction between various aryl aldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one and malononitrile. The method is a facile, inexpensive, practical and highly efficient one to obtain target compounds. The chemical structures of all compounds were characterized by FT-IR, FT-(CNMR)-C-13 and FT-(HNMR)-H-1, MS spectroscopy and also elemental analyses data. Furthermore, the purity of all novel compounds was checked by HPLC. In addition, both molecular modelling studies and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMETox) prediction nominated all compounds as good acetylcholinesterase inhibitors to the potential treatment of Alzheimer, Parkinson and Autism diseases that among them compound 4f showed the best activity against acetylcholinesterase enzyme.