Browsing by Author "Raji, Sarah Mohammed Jaafar"

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In Silico Screening of Multi Target Drug for Alzheimer'sdisease and Parkinson's Disease Using Pharmacophore-Baseddrug Discovery Approach
(Kadir Has Üniversitesi, 2019) Raji, Sarah Mohammed Jaafar; Yelekçi, Kemal
Research on neurodegenerative diseases (NDD), commonly known as Alzheimer's and Parkinson's disease are the most important concern in this aging society. Among the other causes the main suspected reasons are the production and precipitation of the beta amyloid plaques as well as the decrease of acetyl and butyryl choline neurotransmitter in the brain. This eventually results in dementia in older people. APOE (apolipoprotein) alleles (genes) are very important for the genetic determination of Alzheimer disease (AD). Those individuals carrying APOE ε4 allele have the high risk of getting AD comparing with the people having more common ε3 and ε2 alleles. MK-8931(secretase inhibitor), CSP-1103, Pioglitazone, Saracatinib, Aducanumab, Solanezumab, etc. are the drugs generally categorized as disease-modifying drugs which help to postpone the symptoms. However, modifying drugs can entirely reduce the possibility of Alzheimer disease (AD) evolution. Whereas, Parkinson's disease (PD) is a type of degenerative disorder which occurs in the central nervous system (CNS) that mainly influence the motor system. Mutations in specific genes like SNCA, LRRK2, GBA, PRKN, PINK1, PARK7, etc. are the reason for about 5-10& \%\ of PD cases. In this study, we are aiming to obtain some more potent novel inhibitors than that of the current approved drugs for Alzheimer's (target enzyme acetylcholine esterase enzyme pdb code: 1EVE) and Parkinson's disease (target enzyme monoamine oxidase enzyme pdb code: 2V5Z) using molecular modeling and in silico screening methods. Molecular modeling and docking studies are performed in this research to obtain the preferable candidates have inhibitory effect against both diseases. Wherefore, pharmacophore approach was applied by using zinc pharma database compounds to achieve the aim of this study. After several screening analysis techniques, cross docking procedure was applied on the final 15 compounds that obtained from (AD) and (PD). All compounds shown a significant binding energy with target protein, 12 compounds have had a dual effecting on both diseases and only 3 compounds were identified a selectivity against 1EVE target of acetylcholinesterase enzyme. Eventually all compounds were subjected to ADME assay and Toxicity by using ADMET SAR tool.