In Silico Drug Design and Analysis of Dual Amyloid-Beta and Tau Protein-Aggregation Inhibitors for Alzheimer's Disease Treatment.

ABSTRACT: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that gradually leads to the state of dementia. The main features of AD include the deposition of amyloid-beta peptides (Aβ), forming senile plaques, and the development of neurofibrillary tangles due to the accumulation of hyperphosphorylated Tau protein (p-tau) within the brain cells. In this report, seven dual-inhibitor molecules (L_1-7) that can prevent the aggregation of both Aβ and p-tau are suggested. The drug-like features and identification of the target proteins are analyzed by the in silico method. L_1-7 show positive results in both Blood-Brain Barrier (BBB) crossing and gastrointestinal absorption, rendering to the results of the permeation method. The molecular docking test performed for L_1-7 shows binding energies in the range of -4.9 to -6.0 kcal/mol towards Aβ, and -4.6 to -5.6 kcal/mol for p-tau. The drug's effectiveness under physiological conditions is assessed by the use of solvation models on the investigated systems. Further, the photophysical properties of L_1-3 are predicted using TD-DFT studies.

SUBMITTER: Job N 

PROVIDER: S-EPMC9919237 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature