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Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

[ Vol. 18 , Issue. 5 ]

Author(s):

Vanessa Silva Gontijo, Flávia P. Dias Viegas, Cindy Juliet Cristancho Ortiz, Matheus de Freitas Silva, Caio Miranda Damasio, Mayara Chagas Rosa, Thâmara Gaspar Campos, Dyecika Souza Couto, Kris Simone Tranches Dias and Claudio Viegas*   Pages 348 - 407 ( 60 )

Abstract:


Neurodegenerative Diseases (NDs) are progressive multifactorial neurological pathologies related to neuronal impairment and functional loss from different brain regions. Currently, no effective treatments are available for any NDs, and this lack of efficacy has been attributed to the multitude of interconnected factors involved in their pathophysiology. In the last two decades, a new approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDLs) strategy, has emerged and has been used in the design and for the development of a variety of hybrid compounds capable to act simultaneously in diverse biological targets. Based on the polypharmacology concept, this new paradigm has been thought as a more secure and effective way for modulating concomitantly two or more biochemical pathways responsible for the onset and progress of NDs, trying to overcome low therapeutical effectiveness. As a complement to our previous review article (Curr. Med. Chem. 2007, 14 (17), 1829-1852. https://doi.org/10.2174/092986707781058805), herein we aimed to cover the period from 2008 to 2019 and highlight the most recent advances of the exploitation of Molecular Hybridization (MH) as a tool in the rational design of innovative multifunctional drug candidate prototypes for the treatment of NDs, specially focused on AD, PD, HD and ALS.

Keywords:

Molecular hybridization, multi-target directed ligands, rational drug design, multifunctional drugs, neurodegenerative diseases, MTDLs.

Affiliation:

PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840, Institute of Biomedical Sciences, Federal University of Alfenas, 37133-840, Minas Gerais, PeQuiM-Laboratory of Research in Medicinal Chemistry, Institute of Chemistry, Federal University of Alfenas, 37133-840

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