4-Oxoquinolines and monoamine oxidase: When tautomerism matters

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Mesiti, F (Author) Other; Maruca, A (Author) Other; Silva, V (Author) Other; Rocca, R (Author) Other; Fernandes, C (Author) Other; Fernando Remiao (Author) FFUP; Uriarte, E (Author) Other; Alcaro, S (Author) Other; Gaspar, A (Author) Other; Fernanda Borges (Author) FCUP

Journal

Title: European Journal of Medicinal Chemistry

Vol. 213

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00T-CGB

DOI: 10.1016/j.ejmech.2021.113183

Abstract (EN): 4-Oxoquinoline derivatives have been often used in drug discovery programs due to their pharmacological properties. Inspired on chromone and 4-oxoquinoline chemical structure similarity, a small series of quinoline-based compounds was obtained and screened, for the first time, toward human monoamine oxidases isoforms. The data showed the N-(3,4-dichlorophenyl)-1-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 10 was the most potent and selective MAO-B inhibitor (IC50 = 5.30 +/- 0.74 nM and SI: >= 1887). The data analysis showed that prototropic tautomerism markedly influences the biological activity. The unequivocal characterisation of the quinoline tautomers was performed to understand the attained data. To our knowledge, there have been no prior reports on the characterisation of quinolone tautomers by 2D NMR techniques, namely by H-1-N-15 HSQC and H-1-N-15 HMBC, which are proposed as expedite tools for medicinal chemistry campaigns. Computational studies on enzyme-ligand complexes, obtained after MM-GBSA calculations and molecular dynamics simulations, supported the experimental data.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11