Design and synthesis of chromone-based monoamine oxidase B inhibitors with improved drug-like properties

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Reis, J (Author) Other; Fernandes, C (Author) Other; Salem, H (Author) Other; Maia, M (Author) Other; Tome, C (Author) Other; Benfeito, S (Author) Other; Teixeira, J (Author) Other; Oliveira, PJ (Author) Other; Uriarte, E (Author) Other; Ortuso, F (Author) Other; Alcaro, S (Author) Other; Bagetta, D (Author) Other; Fernando Cagide (Author) FCUP; Fernanda Borges (Author) FCUP

Journal

Title: European Journal of Medicinal Chemistry

Vol. 239

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00W-RHE

DOI: 10.1016/j.ejmech.2022.114507

Abstract (EN): The absence of disease modifying drugs in Parkinson's disease therapy urges for new chemical entities acting on relevant PD-associated biological targets. As a result, developing selective and reversible inhibitors targeting MAO-B is still a desirable line of therapeutic research. Within this framework, a small library of chromone derivatives was synthesized and screened towards human monoamine oxidases. Structural modifications on the chromone 3-phenylcarboxamide resulted in potent MAO-B inhibitors with an improved drug-like profile, and for the first time we obtained potent and selective chromone 2-phenylcarboxamides acting in the low nanomolar range. Compounds 5-hydroxy-4-oxo-N-phenyl-4H-chromene-3-carboxamide (38) (IC50 = 13.0 nM) and N-(4-chlorophenyl)-5-hydroxy-4-oxo-4H-chromene-3-carboxamide (41) (IC50 = 8.3 nM) stood out as reversible, potent, selective and non-cytotoxic MAO-B inhibitors bearing a favourable drug-like profile. Both compounds displayed cytoprotective effects towards iron(III) oxidative stressor.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12