New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors

A new set of hybrid derivatives bearing pyrazole and coumarin scaffold 3a-f was synthesized and confirmed by different spectroscopic techniques (H-1 NMR, C-13 NMR, FT-IR) and mass spectrometry. This study aimed to evaluate the inhibitory activity of new derivatives against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using Galanthamine as standard drugs. In vitro studies showed that compounds 3e and 3f were the most effective showing high potential AChE inhibitory activities with respective IC50 values of 4.41 +/- 0.53 and 5.04 +/- 0.96 mu g/ml. Compounds 3a and 3b were found to be the best butyrylcholinesterase inhibitor with an IC50 value comparable to that of the standard drugs. All the newly synthesized derivatives 3a-f are evaluated for their antioxidant activity and showed good activity. Molecular docking study was also carried to get insights into binding interactions of synthesized compounds to act as AChE and BChE inhibitors. The docking study of compound 3e with AChE enzyme showed that PAS are occupied by the ligand. In silico predictions of toxicity analysis indicated that these compounds should have good oral bioavailability. (C) 2021 Elsevier B.V. All rights reserved.