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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

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

Journal

Title: ChemistrySelect

Vol. 4

Pages: 7698-7703

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6