Design, synthesis and biological evaluation of honokiol derivatives as influenza neuraminidase inhibitors

Abstract

Honokiol, a natural polyphenol, which was reported to have satisfactory influenza neuraminidase (NA) inhibitory activity, was structurally modified. Twenty-three compounds were synthesized and the ortho-effects in the epoxidation and hydrolyzation reactions were studied. The derivatives were evaluated for NA inhibitory activity and the benzoylhydrazone derivatives showed much better anti-NA activity than honokiol. Structure-activity relationship analysis suggested that the polyphenols exhibited better anti-NA activity than monophenols and biphenols. Furthermore, probable binding mode of drug with target revealed that the most active compound had much stronger interactions with the active site of NA than honokiol suggesting the potent anti-influenza virus activity.

Graphical Abstract

Keywords:

• Influenza
• neuraminidase inhibitor
• honokiol
• polyphenol
• structure-activity relationship

Acknowledgments

The authors are thankful to the Institute of Materia Medica of Chinese Academy of Medical Sciences and Peking Union Medical College for providing the biological activity assays.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the National Natural Science Fundation of China (No. 21442014) and the National Natural Science Foundation of China (No. 81673480).