Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents.
Eur J Med Chem
; 198: 112360, 2020 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-32403018
ABSTRACT
Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent inhibitory effects on fluconazole-resistant fungi. Subsequently, preliminary mechanistic studies indicated that the representative compound A03 had a strong inhibitory effect on C.alb. CYP51. Moreover, the target compounds could prevent the formation of fungi biofilms. Further hemolysis test verified that potential compounds had higher safety than miconazole. In addition, molecular docking study provided the interaction modes between the target compounds and C.alb. CYP51. These results strongly suggested that some target compounds are promising as novel antifungal drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organosselênicos
/
Miconazol
/
Antifúngicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article