4-Oxoquinolines and monoamine oxidase: When tautomerism matters

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

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

Revista

Título: European Journal of Medicinal Chemistry

Vol. 213

ISSN: 0223-5234

Editora: Elsevier

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 6 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11