Executive Summary : | Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunctions and memory deficits. Current drugs like dopezil, rivastigmine, galantamine, and memantine act on cholinesterase in the brain, reducing amyloid-beta (Aβ) aggregation. Cholinesterase inhibitors are widely used for AD treatment. The β-secretase (BACE1) plays a significant role in AD development. Recently, Aducanumab and Lecanemab have been approved as disease-modifying agents in AD. This study aims to explore the multitarget directed ligands (MTDLs) approach to overcome the complexity of disease conditions. Plant-based drugs like galantamine, physostigmine, and rivastigmine act as cholinesterase inhibitors and improve memory in AD patients. Piperine, a plant-based drug, has shown therapeutic effects in neurological disorders. However, piperine exhibited less potency towards cholinesterases and BACE1 compared to donepezil. To improve the effect of piperine, substituted oxadiazole and piperazine group substituted compounds were designed. Piperine semisynthetic hybrids will be synthesized to achieve multi-target effects and improve the potency of compounds for AD management. The compounds will be evaluated through in vitro experiments, ex vivo experiments, and histopathological sections from the hippocampus region. The studies will suggest designed alkaloid piperine derivatives for multitarget action and neuroprotective properties in AD. |