8-Hydroxyquinoline-based anti-Alzheimer multimodal agents

The concept of multitarget-directed ligands (MTDLs) has attracted considerable interest in the development of agents against Alzheimer’s disease. Cathepsin B, a cysteine protease, and butyrylcholinesterase, a serine hydrolase, play important function in the development and progression of Alzheimer’s disease. We present herein the evaluation of 8-hydroxyquinoline-based analogues with activities against butyrylcholinesterase and β-secretase activity of cathepsin B. Furthermore, inhibition of amyloid β aggregation, chelation of copper and zinc ions coupled with antioxidative properties and safe cytotoxicity profile of ( 1R , 2S )- N -ethyl-2-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl]amino]cyclohexane-1-carboxamide suggest that this derivative is a good starting point for optimization towards an effective multifunctional ligand. Graphic abstract