Design, Synthesis and Biological Evaluation of Novel Ligands as Potential Anti-Alzheimer’s Agents

Memory problems in elderly people could be symptoms of Alzheimer s disease (AD), an irreversibleneurodegenerative brain disease causing progressive deterioration of memory, thinkingand reasoning skills [1]. AD is a complex multifactor disease that its exact pathogenesis isnot fully clear. Neuropathological studies have demonstrated that the low levels of acetylcholine,-amyloid plaques formation within the brain of AD patients and oxidative damage ofneuronal cells are the key factors for the development of AD [2]. Due to the importance ofmulti-target drugs development for AD therapy and on the basis of above-mentioned findings,we have designed two series of new compounds including benzoheterocycles-based N-benzylpyridinium derivatives and 2,3-dinaminopyridine-coumarin analogs (Fig. 1). The designedcompounds were synthesized and evaluated for multifunctional biological activities includinganti-cholinesterase, Aβ1-42 protein anti-aggregating, and protective effect against H2O2-induced PC12 cell injury, as well as docking study.