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Design of Multi-target Directed Ligands as a Modern Approach for the Development of Innovative Drug Candidates for Alzheimer’s Disease

  • Cindy Juliet Cristancho Ortiz
  • Matheus de Freitas Silva
  • Vanessa Silva Gontijo
  • Flávia Pereira Dias Viegas
  • Kris Simone Tranches Dias
  • Claudio ViegasJr.Email author
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a multi-faceted pathogenesis. So far, the therapeutic paradigm “one-compound-one-target” has failed and despite enormous efforts to elucidate the pathophysiology of AD, the disease is still incurable, with all current medicines only being capable to slow up its progress and ameliorate the quality of life of the patients. The multiple factors involved in AD include amyloid aggregation to form insoluble neurotoxic plaques of Aβ, hyperphosphorylation of tau protein, oxidative stress, calcium imbalance, mitochondrial dysfunction, deterioration of synaptic transmission, and neuronal loss. These factors together accentuate changes in the central nervous system (CNS) homeostasis, starting a complex process of interconnected physiological damage, leading to cognitive and memory impairment and neuronal death. A recent approach for the rational design of new drug candidates, also called multi-target directed ligand (MTDL) approach, has gained increasing attention by many research groups, which have developed a variety of hybrid compounds acting simultaneously on diverse biological targets. In this chapter, we aimed to show some recent advances during the last decade and examples of the exploitation of MTDL approach in the rational design of novel drug candidate prototypes for the treatment of AD.

Keywords

Alzheimer’s disease Multifunctional drugs Multi-target directed drugs Multi-target drugs Neurodegenerative disorders Rational drug design 

Notes

Acknowledgements

The authors are greatul to the Brazilian Agencies CNPq (#454088/2014-0, #400271/2014-1, #310082/2016-1), FAPEMIG (#CEX-APQ-00241-15), FINEP, INCT-INOFAR (#465.249/2014-0), PRPPG-UNIFAL, and CAPES for financial support and fellowships.

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Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  • Cindy Juliet Cristancho Ortiz
    • 1
    • 2
  • Matheus de Freitas Silva
    • 1
    • 2
  • Vanessa Silva Gontijo
    • 1
    • 2
  • Flávia Pereira Dias Viegas
    • 1
  • Kris Simone Tranches Dias
    • 1
  • Claudio ViegasJr.
    • 1
    • 2
    Email author
  1. 1.PeQuiM, Laboratory of Research in Medicinal ChemistryInstitute of Chemistry, Federal University of AlfenasAlfenasBrazil
  2. 2.Programa de Pós-Graduação em QuímicaFederal University of AlfenasAlfenasBrazil

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