Alzheimer’s Disease (AD) is
the most prevalent age-related dementia.
AD can be caused by abnormal processing of amyloid precursor protein (APP) or
by oxidative stress or may be due to the actions of kinases or the degeneration and loss of functions of neurons in the brain. Although
various treatments have already gained success in the in vitro studies, however, till now not a single satisfactory drug has been proven
that can cure this disease permanently till now. In this
study, the best possible drug has been determined from a group of drug
molecules using methods of molecular docking. Molecular docking is a
computational approach which helps to
determine the best molecule from a group of molecules which may bind with the highest affinity with the intended target by mimicking the original biological
environment in a computer. The tested drug molecules in this experiment are the disease modifying agents, capable of
inhibiting a particular protein involving in the AD pathway. Eight drug
molecules (ligands)-memantine (-4.075 Kcal/mol), hymenialdisine (-8.079 Kcal/mol), tideglusib (-6.445 Kcal/mol), kenpaullone (-7.545 Kcal/mol), dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imidazol] (-4.742 Kcal/mol), harmine (-7.57 Kcal/mol), harmol
(-6.583 Kcal/mol) and 1-Methyl-4-Phenylpyridinium (-5.214 Kcal/mol),
have been docked successfully against four
targets (proteins)-N-Methyl-D-Aspartate Receptor (NMDAR), glycogen synthase kinase-3β (GSK-3β), beta-secretase (β-secretase) and dual specificity
tyrosine (Y)-phosphorylation-regulated kinase 1A (DYR-K1A) in
this experiment which are intended
targets in current AD treatment approaches. Investigation of docking results, druglikeness
properties and ADME/T testing results
suggest that the best findings of this experiment are memantine,
hymenialdisine, dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imi- dazol]
and harmol, that could be the best possible drugs for the treatment of AD.