Design, synthesis and biological evaluation of indolizine derivatives as HIV-1 VIF-ElonginC interaction inhibitors.
Mol Divers
; 17(2): 221-43, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23378232
ABSTRACT
The HIV-1 viral infectivity factor (VIF) protein is essential for viral replication. VIF recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. Thus, the A3G-Vif-E3 complex represents an attractive target for the development of novel anti-HIV drugs. In this study, we describe the design and synthesis of indolizine derivatives as VIF inhibitors targeting the VIF-ElonginC interaction. Many of the synthesized compounds exhibited obvious inhibition activities of VIF-mediated A3G degradation, and 5 compounds showed improvement of activity compared to the known VIF inhibitor VEC-5 (1) with IC(50) values about 20 µM. The findings described here will be useful for the development of more potent VIF inhibitors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
VIH-1
/
Fármacos Anti-VIH
/
Citidina Desaminasa
/
Productos del Gen vif del Virus de la Inmunodeficiencia Humana
/
Indolizinas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Divers
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
País de afiliación:
China