SAR Studies and Biological Characterization of a Chromen-4-one Derivative as an Anti-Trypanosoma brucei Agent

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Borsari, C (Autor) Outra; Santarem, N (Autor) Outra; Macedo, S (Autor) Outra; Dolores Jimenez Anton, MD (Autor) Outra; Torrado, JJ (Autor) Outra; Isabel Olias Molero, AI (Autor) Outra; Corral, MJ (Autor) Outra; Tait, A (Autor) Outra; Ferrari, S (Autor) Outra; Costantino, L (Autor) Outra; Luciani, R (Autor) Outra; Ponterini, G (Autor) Outra; Gul, S (Autor) Outra; Kuzikov, M (Autor) Outra; Ellinger, B (Autor) Outra; Behrens, B (Autor) Outra; Reinshagen, J (Autor) Outra; Maria Alunda, JM (Autor) Outra; Anabela Cordeiro da Silva (Autor) FFUP; Costi, MP (Autor) Outra

Revista

Título: Acs Medicinal Chemistry Letters

Vol. 10

Páginas: 528-533

ISSN: 1948-5875

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 3 Citações

Outras Informações

ID Authenticus: P-00Q-F80

DOI: 10.1021/acsmedchemlett.8b00565

Abstract (EN): Chemical modulation of the flavonol 2-(benzo[d] [1,3]dioxo1-5-y1)-chromen-4-one (1), a promising anti-Trypanosomatid agent previously identified, was evaluated through a phenotypic screening approach. Herein, we have performed structure activity relationship studies around hit compound 1. The pivaloyl derivative (13) showed significant anti-T. brucei activity (EC50 = 1.1 1iM) together with a selectivity index higher than 92. The early in vitro ADME-tox properties (cytotoxicity, mitochondria] toxicity, cytochrome P450 and hERG inhibition) were determined for compound 1 and its derivatives, and these led to the identification of some liabilities. The 1,3-benzodioxole moiety in the presented compounds confers better in vivo pharmacokinetic properties than those of classical flavonols. Further studies using different delivery systems could lead to an increase of compound blood levels.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11