3-Arylcoumarins as highly potent and selective monoamine oxidase B inhibitors: Which chemical features matter?

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Mellado, M (Author) Other; Mella, J (Author) Other; Gonzalez, C (Author) Other; Vina, D (Author) Other; Uriarte, E (Author) Other; Matos, MJ (Author) FCUP

Journal

Title: Bioorganic Chemistry

Vol. 101

ISSN: 0045-2068

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00S-8D6

DOI: 10.1016/j.bioorg.2020.103964

Abstract (EN): Monoamine oxidase B inhibitory activity is closely regulated by the interaction of the small molecules with the enzyme. It is therefore desirable to use theoretical approaches to design rational methods to develop new mo-lecules to modulate specific interactions with the protein. Here, we report such methods, and we illustrate their successful implementation by studying six synthetized 3-arylcoumarins (71-76) based on them. Monoamine oxidase B inhibition is essential to maintain the balance of dopamine, and one of its major functions is to combat dopamine degradation, a phenomenon linked to Parkinson's disease. In this work, we study small-molecule inhibitors based on the 3-arylcoumarin scaffold and their monoamine oxidase B selective inhibition. We show that 3D-QSAR models, in particular CoMFA and CoMSIA, and molecular docking approaches, enhance the probability to find new interesting inhibitors, avoiding very costly and time-consuming synthesis and biological evaluations.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10