چكيده به لاتين
Alzheimer's is the most common type of dementia in the world today that has no specific treatment and the number of patients and its annual mortality is increasing dramatically. So far, no comprehensive computational study has been performed on the effective compounds and it was concluded that in this study, a total of 4101 compounds will be subjected to a comprehensive and complete study. After collecting data from the literature, they were divided based on groups of compounds derived. The groups that are the most effective drugs available for the treatment of this disease; Donepezil, Rivastigmine, Galantamine, and Tacrine. A quantitative study of the structure-activity relationship (QSAR) using half-concentration values effective in inhibiting the activity of cholinesterase, and beta-secretase, which are the most important enzymes in the mechanism of this disease, as well as the percentage of inhibition of amyloid beta peptide aggregations, other causes of the disease, were discussed. After optimizing the compounds, molecular descriptors were extracted and some were selected based on determinant tables, and then SR-RF, SR-MLP, SR-SVR, and SR-MLR prediction models were constructed. Examining the available data for four types of cholinesterase in each class of derivatives and beta-secretase enzyme, as well as inhibitors of amyloid-beta aggregation, the most effective descriptors, were used in optimizing the structure of compounds and 6 new compounds with the best inhibitory effect and the lowest predicted toxicity were designed and introduced. Simulation and docking studies of these compounds with the place of the effect of each showed that the new compounds have good stability during the simulation and form good bonds with the active site and nano oxidants as carriers.
