文摘
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 $\upmu $ M. The findings described here will be useful for the development of more potent VIF inhibitors.