Antiviral activity of diarylheptanoid stereoisomers against respiratory syncytial virus in vitro and in vivo.

Abstract

We previously showed that (5S)-5-hydroxy-7-(4-hydroxyphenyl)-1-phenylhept-3-one (AO-0011) and (5S)-5-methoxy-1,7-diphenylhept-3-one (AO-0016) isolated from Alpinia officinarum exhibited stronger anti-influenza virus activity and anti-respiratory syncytial virus (RSV) activity, respectively, than the other isolated diarylheptanoids. In this study, we synthesized an enantiomer (AO-0503) and racemate (AO-0504) of AO-0011 and an enantiomer (AO-0514) of AO-0016. The anti-RSV activities of the three stereoisomers (AO-0503, AO-0504, and AO-0514) and AO-0011 were examined in vitro and in vivo to evaluate the stereoisomeric effect on anti-RSV activity. In a plaque reduction assay using human epidermoid carcinoma cells, all four diarylheptanoids significantly exhibited anti-RSV activity, and AO-0514 and AO-0016 exhibited stronger anti-RSV activity than AO-0503, AO-0504, and AO-0011. In a murine RSV infection model, all four diarylheptanoids with anti-RSV activity in vitro were also significantly effective in reducing virus titers in the lungs of RSV-infected mice. In the histopathological analysis of RSV-infected lungs, the oral administration of even AO-0514, which showed the lowest reduction of virus titers in the lungs, was significantly effective in reducing the infiltration of lymphocytes and in reducing the interferon-γ level, which is a marker of severity of pneumonia due to RSV infection, in bronchoalveolar lavage fluids prepared from RSV-infected mice. Although the stereoisomeric effects of diarylheptanoids on anti-RSV activity varied moderately, all four diarylheptanoids examined were suggested to ameliorate pneumonia and have a potential anti-RSV activity in vivo. They are possibly mother compounds for the development of an anti-RSV drug in the future.

• Authors: Katsuhiko Konno, Motofumi Miura, Masaharu Toriyama, Shigeyasu Motohashi, Rie Sawamura, Wataru Watanabe, Hiroki Yoshida, Masahiko Kato, Ryuichi Yamamoto, Ken Yasukawa, Masahiko Kurokawa
• Journal: Journal of natural medicines (J Nat Med) Vol. 67 Issue 4 Pg. 773-81 (Oct 2013) ISSN: 1861-0293 [Electronic] Japan
• PMID: 23344928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Diarylheptanoids
• Interferon-gamma

Topics

• Alpinia (chemistry)
• Animals
• Antiviral Agents (chemistry, pharmacology, therapeutic use)
• Cell Line, Tumor
• Diarylheptanoids (chemistry, pharmacology, therapeutic use)
• Female
• Humans
• Interferon-gamma (metabolism)
• Lung (pathology, virology)
• Mice
• Mice, Inbred BALB C
• Respiratory Syncytial Virus Infections (drug therapy, pathology)
• Respiratory Syncytial Viruses (drug effects)
• Stereoisomerism