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 de...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.展开更多
文摘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.
