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

Author:

Job Nisha1ORCID,Thimmakondu Venkatesan S.2ORCID,Thirumoorthy Krishnan1ORCID

Affiliation:

1. Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India

2. Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA

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 (L1–7) 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. L1–7 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 L1–7 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 L1–3 are predicted using TD-DFT studies.

Funder

VIT SEED

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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