Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America
Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni
Article type: Research Article
Authors: Chaparro, Diegoa; b | Flores-Gaspar, Arelib; * | Alí-Torres, Jorgea; *
Affiliations: [a] Departamento de Química, Universidad Nacional de Colombia, Bogotá, Colombia | [b] Departamento de Química, Universidad Militar Nueva Granada, Cajicá, Colombia
Correspondence: [*] Correspondence to: Jorge Alí-Torres, Av. Cra 30 N 45-03, Bogotá, Colombia. Tel.: +57 1 3165000/ Ext. 10608; E-mail: jialit@unal.edu.co; Areli Flores-Gaspar, E-mail: areli.flores@unimilitar.edu.co.
Abstract: Background:Redox active metal cations, such as Cu2 +, have been related to induce amyloid plaques formation and oxidative stress, which are two of the key events in the development of Alzheimer’s disease (AD) and others metal promoted neurodegenerative diseases. In these oxidative events, standard reduction potential (SRP) is an important property especially relevant in the reactive oxygen species formation. Objective:The SRP is not usually considered for the selection of drug candidates in anti-AD treatments. In this work, we present a computational protocol for the selection of multifunctional ligands with suitable metal chelating, pharmacokinetics, and redox properties. Methods:The filtering process is based on quantum chemical calculations and the use of in silico tools. Calculations of SRP were performed by using the M06-2X density functional and the isodesmic approach. Then, a virtual screening technique (VS) was used for similar structure search. Results:Protocol application allowed the assessment of chelating, drug likeness, and redox properties of copper ligands. Those molecules showing the best features were selected as molecular scaffolds for a VS procedure in order to obtain related compounds. After applying this process, we present a list of candidates with suitable properties to prevent the redox reactions mediated by copper(II) ion. Conclusion:The protocol incorporates SRP in the filtering stage and can be effectively used to obtain a set of potential drug candidates for AD treatments.
Keywords: Alzheimer’s disease, antioxidants, computer-aided drug design, density functional theory (DFT) calculations, drug discovery, metal complexes, redox
DOI: 10.3233/JAD-200911
Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S179-S193, 2021
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl