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In Silico Studies Applied to Natural Products with Potential Activity Against Alzheimer’s Disease

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Computational Modeling of Drugs Against Alzheimer’s Disease

Part of the book series: Neuromethods ((NM,volume 132))

Abstract

The neurodegenerative disease, named Alzheimer’s disease (AD) after its discoverer, is today considered the most common form of dementia. AD represents 60–70% of dementia cases in patients of 65 years of age or older. It leads to complete dementia and death. AD’s causes are unknown, yet it evidences mutations in several genes, factors such as the amyloid precursor protein (APP), presenilins (PS1, PS2), apolipoprotein E, etc. In silico methods or CADD (computer-aided drug design) studies are increasingly being used in both industry and universities. They involve an understanding of the molecular interactions from both qualitative and quantitative points of view. These methods generate and manipulate three-dimensional (3D) molecular structures; calculate descriptors and the independent molecular properties, followed by model constructions; and employ other tools that encompass computational drug research. Analysis of the molecular structure of a given system allows relevant information to be extracted and to predict the potential of bioactive compounds.

We found mainly research on the inhibitory activity of flavonoids, alkaloids, and xanthones in key enzymes of the biochemical changes that occur in AD: acetylcholinesterase (AChE; EC 3.1.1.7), butyrylcholinesterase (BChE; EC 3.1.1.8), and monoamine oxidase (MAO; EC 1.4.3.4). Recent research has used QSAR and docking for selection of multifunctional compounds that are drugs on multitargets. The multitarget QSAR model can simultaneously predict activity or classify compounds as actives or inactives against different targets, such as the proteins (amyloid-A4 protein (ABPP), glycogen synthase kinase-3 alpha, glycogen synthase kinase-3 beta (GSK-3β), monoamine oxidase B (MAO-B), and presenilin-1 (PSN-1)).

This chapter will discuss several in silico studies reported considering the complexity of this neurodegenerative disease, the possible multifactorial origin, and the pharmacological potential of natural products.

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Acknowledgments

The authors wish to acknowledge the ConselhoNacional de DesenvolvimentoCientífico e Tecnológico (CNPq).

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Authors and Affiliations

  1. Federal University of Paraíba, Health Center, 50670-910, João Pessoa, PB, Brazil

    Luciana Scotti & Marcus T. Scotti

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  1. Luciana Scotti
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  2. Marcus T. Scotti
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Correspondence to Luciana Scotti .

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Editors and Affiliations

  1. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India

    Kunal Roy

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Scotti, L., Scotti, M.T. (2018). In Silico Studies Applied to Natural Products with Potential Activity Against Alzheimer’s Disease. In: Roy, K. (eds) Computational Modeling of Drugs Against Alzheimer’s Disease. Neuromethods, vol 132. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7404-7_18

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  • DOI: https://doi.org/10.1007/978-1-4939-7404-7_18

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