Novel trypanocidal thiophen-chalcone cruzain inhibitors: structure- and ligand-based studies.
Future Med Chem
; 14(11): 795-808, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35543430
ABSTRACT
Background:
Chagas disease is a neglected tropical disease that affects millions of people worldwide and for which no effective treatment is available. Materials &methods:
17 chalcones were synthesized, for which the inhibition of cruzain and trypanocidal activity were investigated.Results:
Chalcone C8 showed the highest cruzain inhibitory (IC50 = 0.536 µm) and trypanocidal activity (IC50 = 0.990 µm). Molecular docking studies showed interactions involving Asp161 and the thiophen group interacting with the S2 subsite. Furthermore, quantitative structure-activity relationship (q2 = 0.786; r2 = 0.953) and density functional theory studies were carried out, and a correlation between the lowest unoccupied molecular orbital surface and trypanocidal activity was observed.Conclusion:
These results demonstrate that these chalcones are worthwhile hits to be further optimized in Chagas disease drug discovery programs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
/
Trypanosoma cruzi
/
Chalcona
/
Doença de Chagas
/
Chalconas
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil