Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.
Bioorg Med Chem Lett
; 28(9): 1647-1651, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29609908
ABSTRACT
A series of natural products-based phenyl sulfone derivative and their property-based analogues were investigated as potential growth inhibitors of Trypanosoma brucei. Trypanosoma brucei is a kinetoplastid protozoan parasite that causes trypanosomiasis. In this work, we found that nopol- and quinoline-based phenyl sulfone derivative were the most active and selective for T. brucei, and they were not reactive towards the active thiol of T. brucei's cysteine protease rhodesain. A thiol reactive variant of the quinoline-based phenyl sulfone was subsequently investigated and found to be a moderate inhibitor of rhodesain. The quinoline-based compound that is not reactive towards rhodesain can serve a template for phenotypic-based lead discovery while its thiol-active congener can serve as template for structure-based investigation of new antitrypanosomal agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Sulfonas
/
Tripanossomicidas
/
Trypanosoma brucei brucei
/
Produtos Biológicos
/
Descoberta de Drogas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article