In-silico studies of some potent hybrid compounds against Alzheimer's disease through virtual screening, simulation techniques, and pharmacokinetic endowment

• Published in: Biocatalysis and agricultural biotechnology 2023-11, Vol.54, p.102941, Article 102941
• Main Authors: Ajala, Abduljelil, Uzairu, Adamu, Shallangwa, Gideon A., Abechi, Stephen E.
• Format: Article
• Language: English
• Subjects: absorption; agricultural biotechnology; Alzheimer disease; biocatalysis; brain; computer simulation; dopamine; etiology; excretion; hydrogen; hydrophobicity; ligands; neurotransmitters; norepinephrine; pharmacokinetics; prediction; scientists; therapeutics; toxicity
• ISSN: 1878-8181; 1878-8181
• DOI: 10.1016/j.bcab.2023.102941

Complications in the etiology of Alzheimer Disease (AD) as being a concern among the research scientist and medicinal community. Hybrids compounds with multi-targeted property have been reported in the literature to be effective in curing/hindering the menace of this disease. In this research, virtual screenings of potent, non-toxic hybrid compounds will be performed, carrying out simulations on the screened compounds and predicting the druggability of the screened compounds and these were the goals of this study. Computational methods have been used to solve this problem by applying in-silico screening, simulation techniques, and pharmacokinetic prediction of therapeutic inhibitors capable of preventing or hindering the atrocities imposed by this deadly disease. Twenty-five hybrid compounds were subjected to virtual screening, simulation, and pharmacokinetic assessment. Ten of these compounds showed docking scores with strong binding affinities to enzymes and receptors, forming strong contacts with proteins. The inhibitor docking results were far better than those of the reference compound, with a docking score of −26.30 kcal/mol. The interactions showed similar amino acids in the screened compounds, such as ASN349, PHE168, and SER67, which function as brain signal transmitters and neurotransmitters (norepinephrine and dopamine), and in Alzheimer's disease (AD) treatment, which interact with the ligands through hydrogen and hydrophobic bonds. In addition, the pharmacokinetic and absorption, distribution, metabolism, excretion, and toxicity (ADMET-ox) predictions revealed that all the virtually screened compounds were endowed with therapeutic ability as anti-AD agents. The results determined the possible interactions and their characteristics at the atomic level, and the pharmacokinetic predictions were excellent. Neuroscientists should proceed with further clinical tests, such as in-vivo and in-vitro tests, to ascertain whether these inhibitors meet their targets.