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Computational Modeling of Drugs for Alzheimer’s Disease: Design of Serotonin 5-HT6 Antagonists

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Computational Modeling of Drugs Against Alzheimer’s Disease

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

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Abstract

The 5-hydroxytryptamine receptor 6 (5-HT6R) represents one of the most avowed targets for alleviating cognitive, learning, and memory deficits related to Alzheimer’s disease (AD). Ligand- and structure-based computational modeling methods serve as main tools at the initial stages of drug discovery projects to underlie and to understand small molecule targeting of the receptor. Here, we describe the currently known 5-HT6R antagonists in clinical trials and at discovery stages. We analyze existing ligand-based information and disposable pharmacophore models, quantitative structure-activity relationship methods, usable crystal structure templates, homology models, and molecular docking approaches. Our goal is to provide the reader with guidelines on how to utilize the existing knowledge and ligand- and structure-based methods for the design of new 5-HT6R antagonists and to highlight advantages and limitations of corresponding approaches and computational modeling tools in the field of 5-HT6R drug design.

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Acknowledgments

The authors participate in the European Cooperation in Science and Technology (COST) Action CM1207 – GPCR-Ligand Interactions, Structures, and Transmembrane Signalling: a European Research Network (GLISTEN). This work was supported by the National Brain Research Program KTIA-NAP-13-1-2013-0001. The study was partially supported by the grant OPUS 2014/13/B/NZ7/02210 from the Polish National Science Centre.

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Authors and Affiliations

  1. Medicinal Chemistry Research Group, Research Center for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok krt, 1117, Budapest, Hungary

    Ádám A. Kelemen & György M. Keserű

  2. Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Krakow, Poland

    Stefan Mordalski & Andrzej J. Bojarski

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  1. Ádám A. Kelemen
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  2. Stefan Mordalski
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  3. Andrzej J. Bojarski
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  4. György M. Keserű
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Correspondence to György M. Keserű .

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

    Kunal Roy

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Kelemen, Á.A., Mordalski, S., Bojarski, A.J., Keserű, G.M. (2018). Computational Modeling of Drugs for Alzheimer’s Disease: Design of Serotonin 5-HT6 Antagonists. 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_15

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  • DOI: https://doi.org/10.1007/978-1-4939-7404-7_15

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