Design, Synthesis and Docking Calculations of Prenylated Chalcones as Selective Monoamine Oxidase B Inhibitors with Antioxidant Activity

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Mellado, M (Autor) Outra; Salas, CO (Autor) Outra; Uriarte, E (Autor) Outra; Vina, D (Autor) Outra; Jara Gutierrez, C (Autor) Outra; Matos, MJ (Autor) FCUP; Cuellar, M (Autor) Outra

Revista

Título: ChemistrySelect

Vol. 4

Páginas: 7698-7703

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-00Q-V7Y

DOI: 10.1002/slct.201901282

Abstract (EN): Different natural and synthetic chalcones have exhibited selective inhibition on monoamine oxidase B (MAO-B) activity, demonstrating potential interest for the treatment of neurodegenerative diseases. Herein we report the synthesis of seven new prenylated chalcones (7a-g) obtained from the natural compound 5 (4-hydroxy-3-(3-methylbut-2-en-1-yl)phenylethanone), previously isolated from S. graveolens. Five of these compounds exhibit high inhibition and selectivity against MAO-B, with IC50 values in the low micromolar range. In addition, the antioxidant activity of this series was measured, being three compounds better than the reference, butylated hydroxytoluene (BHT). Compound 7f [(2E)-3-(4-(dimethylamino)phenyl)-1-(4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl)prop-2-en-1-one] proved to be the best compound within the studied series (IC50 MAO-B=8.19 mu M and k DPPH=3.73). Finally, molecular docking was performed to better understand the binding properties of these derivatives. Important features for MAO-B inhibitory activity were observed: hydrogen-bonding interaction between Tyr435 and nearness with Tyr398 and FAD co-factor. Therefore, these molecules are good candidates for the design of a lead compound for Parkinson's disease.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6