Synthesis and anti-BVDV activity of novel δ-sultones in vitro: implications for HCV therapies

Hai-Wei Xu; Ling-Jie Zhao; Huan-Fei Liu; Dan Zhao; Jiao Luo; Xiao-Ping Xie; Wen-Sheng Liu; Jia-Xin Zheng; Gui-Fu Dai; Hong-Min Liu; Long-Hua Liu; Yi-Bo Liang

doi:10.1016/j.bmcl.2014.03.012

Synthesis and anti-BVDV activity of novel δ-sultones in vitro: implications for HCV therapies

Bioorg Med Chem Lett. 2014 May 15;24(10):2388-91. doi: 10.1016/j.bmcl.2014.03.012. Epub 2014 Mar 17.

Authors

Affiliations

¹ New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue DaDao, Zheng zhou, Henan Province 450001, PR China.
² School of Life Sciences, Zhengzhou University, No. 100, KeXue DaDao, Zheng zhou, Henan Province 450001, PR China.
³ School of Life Sciences, Zhengzhou University, No. 100, KeXue DaDao, Zheng zhou, Henan Province 450001, PR China. Electronic address: daiguifu@zzu.edu.cn.
⁴ New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, No. 100, KeXue DaDao, Zheng zhou, Henan Province 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
⁵ College of Chemistry and Molecular Engineering, Zhengzhou University, No. 100, KeXue DaDao, Zheng zhou, Henan Province 450001, PR China.

PMID: 24745970
DOI: 10.1016/j.bmcl.2014.03.012

Abstract

In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0μM and no significant cytotoxicity. Among them, the ortho bromosubstituted derivative 4f (EC50=0.12μM) showed better antiviral activity than other derivatives and was 10 fold more that of than positive control ribavirin (EC50=1.3μM). BVDV is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. The above results provided a novel candidate for the development of anti-HCV agents.

Keywords: Anti-BVDV; Anti-HCV; CSIC reaction; Lactone; Sultone; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology*
Cattle
Diarrhea Viruses, Bovine Viral / drug effects*
Disease Models, Animal
Drug Design
Hepacivirus / drug effects*

Substances

Antiviral Agents