Synthesis, Docking and Evaluation of Novel Pyrazole Carboxamide Derivatives as Multifunctional Anti-Alzheimer's Agents

Alzheimer’s disease (AD) is a major public health problem. The dual inhibitors of monoamine oxidase-B (MAO-B) and acetyl cholinesterase (AchE) are reported as effective in treatment of AD. The present research work was planned to design, synthesize and evaluate pyrazole carboxamide derivatives as multifunctional agents for treatment of AD. A series of substituted pyrazole derivatives were synthesized by refluxing chalcone derivatives with substituted semicarbazides and evaluated by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of MAO-B protein. The selected compounds from the in silico studies were evaluated further for their cognition enhancing and AchE inhibitory activity. Compounds 8 and 11 significantly reversed the scopolamine induced amnesia on elevated plus maze (EPM) model and compound 8 was found to be most potent. The selected compounds also significantly reduced AchE activity in brain. These newly designed molecules could act as starting hits for the development of effective and potent multifunctional agents for the potential treatment of AD.