Design, Synthesis, and Activity Evaluation of Novel Benzazole Bifunctional Antifungal Inhibitors with an LDH Carrier.
J Med Chem
; 67(13): 11365-11388, 2024 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-38888292
ABSTRACT
Fungal infections maintain a close relation with the body's immune function. In this study, three series of benzazole compounds were designed as dual-target (PD-L1/CYP51) inhibitors using the skeleton splicing approach; their molecular structures were synthesized and evaluated accordingly. Among them, the compounds 9a-2, 12a-2, and 12b-1 exhibited potent antifungal activity and dual-target inhibition ability. Especially, the compound 12a-2 simultaneously exerted excellent bifunctional effects of fungal inhibition and immune activation. Moreover, a layered double hydroxide (LDH) carrier was also successfully constructed based on an infection microenvironment to improve the bioavailability and the targeting of compound 12a-2. This significantly accelerated the recovery process of deep and shallow fungal infections. In conclusion, this study expanded the development horizon of antifungal drugs and provided a novel drug delivery route for treating fungal infections.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Testes de Sensibilidade Microbiana
/
Antifúngicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
/
J. med. chem
/
Journal of medicinal chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos