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Molecular Diversity

, Volume 17, Issue 2, pp 221–243 | Cite as

Design, synthesis and biological evaluation of indolizine derivatives as HIV-1 VIF–ElonginC interaction inhibitors

  • Wenlin Huang
  • Tao Zuo
  • Hongwei Jin
  • Zhenming Liu
  • Zhenjun Yang
  • Xianghui Yu
  • Liangren ZhangEmail author
  • Lihe Zhang
Full-Length Paper

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

Keywords

VIF–ElonginC interaction inhibition VEC-5 Anti-HIV-1 Indolizine derivatives Structure-activity relationship 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (20972009).

Supplementary material

11030_2013_9424_MOESM1_ESM.pdf (7.8 mb)
Supplementary material 1 (PDF 7967 KB)
11030_2013_9424_MOESM2_ESM.doc (587 kb)
Supplementary material 2 (DOC 587 KB)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Wenlin Huang
    • 1
  • Tao Zuo
    • 2
  • Hongwei Jin
    • 1
  • Zhenming Liu
    • 1
  • Zhenjun Yang
    • 1
  • Xianghui Yu
    • 2
    • 3
  • Liangren Zhang
    • 1
    Email author
  • Lihe Zhang
    • 1
  1. 1.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical SciencesPeking University BeijingChina
  2. 2.National Engineering Laboratory for AIDS Vaccine, College of Life ScienceJilin UniversityChangchunChina
  3. 3.Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life ScienceJilin UniversityChangchunChina

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