Scopus: 3 citations, Web of Science: 1 citations,
Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4-yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors
Di Pietro, O. (Universitat de Barcelona. Laboratori de Química Farmaceùtica)
Alencar, Nelson (Universitat de Barcelona. Facultat de Farmàcia)
Esteban Conde, Gerard (Universitat Autònoma de Barcelona. Institut de Neurociències)
Viayna, Elisabet (Universitat de Barcelona. Laboratori de Química Farmaceùtica)
Szałaj, Natalia (Universitat de Barcelona. Laboratori de Química Farmaceùtica)
Vázquez, Javier (Universitat de Barcelona. Facultat de Farmàcia)
Juárez-Jiménez, Jordi (Universitat de Barcelona. Facultat de Farmàcia)
Sola, Irene (Universitat de Barcelona. Laboratori de Química Farmaceùtica)
Pérez Fernández, Belén (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Solé Piñol, Montserrat (Universitat Autònoma de Barcelona. Institut de Neurociències)
Unzeta López, Mercedes (Universitat Autònoma de Barcelona. Institut de Neurociències)
Muñoz-Torrero López-Ibarra, Diego (Universitat de Barcelona. Laboratori de Química Farmaceùtica)
Luque Garriga, F. Xavier (Universitat de Barcelona. Facultat de Farmàcia)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date: 2016
Abstract: Different azides and alkynes have been coupled via Cu-catalyzed 1,3-dipolar Huisgen cycloaddition to afford a novel family of N1- and C5-substituted 1,2,3-triazole derivatives that feature the propargylamine group typical of irreversible MAO-B inhibitors at the C4-side chain of the triazole ring. All the synthesized compounds were evaluated against human MAO-A and MAO-B. Structure–activity relationships and molecular modeling were utilized to gain insight into the structural and chemical features that enhance the binding affinity and selectivity between the two enzyme isoforms. Several lead compounds, in terms of potency (submicromolar to low micromolar range), MAO-B selective recognition, and brain permeability, were identified. One of these leads (MAO-B IC50 of 3. 54 μM, selectivity MAO-A/MAO-B index of 27. 7) was further subjected to reversibility and time-dependence inhibition studies, which disclosed a slow and irreversible inhibition of human MAO-B. Overall, the results support the suitability of the 4-triazolylalkyl propargylamine scaffold for exploring the design of multipotent anti-Alzheimer compounds endowed with irreversible MAO-B inhibitory activity.
Note: Número d'acord de subvenció MINECO/SAF2014-57094-R
Note: Número d'acord de subvenció AGAUR/2014/SGR-52
Note: Número d'acord de subvenció AGAUR/2014/SGR-1189
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: article ; recerca ; acceptedVersion
Subject: Click-chemistry ; Monoamine oxidase B ; Alzheimer's disease ; Irreversible inhibition
Published in: Bioorganic & medicinal chemistry, Vol. 24 Núm. 20 (October 2016) , p. 4835-4854, ISSN 0968-0896

DOI: 10.1016/j.bmc.2016.06.045


Available from: 2018-11-01
Post-print

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2017-02-03, last modified 2018-07-24



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