Insight into the functional and structural properties of 3-arylcoumarin as an interesting scaffold in monoamine oxidase B inhibition

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Matos, MJ (Author) Other; Vilar, S (Author) Other; García Morales, V (Author) Other; Tatonetti, NP (Author) Other; Uriarte, E (Author) Other; Santana, L (Author) Other; Viña, D (Author) Other

Journal

Title: ChemMedChem

Vol. 9

Pages: 1488-1500

ISSN: 1860-7179

Publisher: Wiley-Blackwell

Indexing

Scopus - 28 Citations

Other information

Authenticus ID: P-00R-0N8

DOI: 10.1002/cmdc.201300533

Abstract (EN): The design, synthesis, pharmacological evaluation, and theoretical studies of a new series of halogenated 3-arylcoumarins were carried out with the aim of finding new structural and biological features. This series displays several alkyl, hydroxy, halogen, and/or alkoxy groups in both benzene rings of the 3-arylcoumarin scaffold. Most of the compounds studied show high affinity and selectivity for the human monoamine oxidase B (hMAO-B) isoenzyme, with IC 50 values in the low nanomolar and picomolar range. Most of the evaluated compounds display higher MAO-B inhibitory activity and selectivity than selegiline (the reference compound). Coumarin 12 (3-(3-bromophenyl)-6- methylcoumarin) is the most active compound (IC50=134 pM), being 140-fold more active than selegiline and showing the highest specificity for hMAO-B. To better understand the structure-activity relationships, docking experiments were carried out on human monoamine oxidase (A and B) structures. Finally, the prediction of passive blood-brain partitioning, based on in silico derived physicochemical descriptors, was performed. Coumarins crossing the barrier: The design and synthesis of a new series of halogenated 3-arylcoumarins are described. Monoamine oxidase A and B in vitro inhibition studies, in silico prediction of passive blood-brain partitioning, and docking calculations showed most of the 3-arylcoumarin compounds to be potent and selective. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Language: English

Type (Professor's evaluation): Scientific