Multitarget Drug Design, Molecular Docking and PLIF Studies of Novel Tacrine−Coumarin Hybrids for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) as a complicated and progressive neurodegenerative disorder is the most common form of dementia and memory loss. On account of the multifactorial etiology of AD, the multi-target-directed ligand (MTDL) approach is a promising method in searching new drug candidates for this disease. Here, in this paper more than 500 tacrine-coumarin hybrids have been designed and drug-likeness, molecular docking and descriptor analysis of them were performed to find out a drug candidate with less toxicity and better binding affinity than tacrine. The docking analysis was carried out using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS) and β-secretase (BACE1) (1W51) enzymes using AutoDock 4.2 and Vina. The promising results were obtained on the types of interactions. Based on docking on three targets and PLIF studies, the compounds that have better results were introduced as good candidates for synthesis. The validity of docking protocols was verified using a set of known active ligands and decoys on these targets.