| Autor: |
Shahid, S. M. A., Kuddus, Mohammad, Ahmed, Mohamed Qumani, Saleem, Mohd, Kausar, Mohd Adnan, Khalid, M. A., Alghassab, Turki Ahmed, Acar, Tolgahan, Alenazi, Fahaad S. H. |
| Předmět: |
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| Zdroj: |
Biochemical & Cellular Archives; Apr2018, Vol. 18 Issue 1, p629-635, 7p |
| Abstrakt: |
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder and is characterized pathologically by the presence of amyloid plaques, extensive neuronal death, and shrinkage of the brain. Amyloid precursor protein (APP) can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). CuBD of Amyloid precursor protein (APP) can strongly bind Cu(II) and reduce it to Cu(I) this can lead to increased copper-mediated neurotoxicity in cultured neurons (White et al. 1999a), presumably through increased oxidative stress or the generation of reactive oxygen species. Role of metal ions in drug targeted proteins such as copper, zinc, and calcium will be discovered in this work. Therefore, anti-aggregatory agents like metal chelators such as Deferiprone, Memantine, Curcumin, Clioquinol and Chrysamine- G have been used in our study which will remove metal ion and thus reducing aggregation of Aβ peptide. In this proposed work, we will build quantitative structure-activity relationship (QSAR) models, with known experimentally verified inhibitors have inhibitory value IC50 against APP. We will dock these inhibitors at the active site of APP using AutoDock software or Molecular Virtual Docker (MVD), which results an energy-based descriptors for QSAR modeling. Multiple Linear Regression models will be generated using energy-based descriptors and inhibitory value IC50, which yield correlation coefficient. Further, new derivatives of potent natural compounds will be identifying using PubChem compound database and dock with active site of APP protein structure. After docking, new compounds having lower binding energy even lower than standard control Drug with APP will be selected as potential candidate drugs for Alzheimer's. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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