Synthesis of Chalcone Derivatives Containing Furan or/and Pyran Ring as Neuraminidase Inhibitors

Abstract

Twenty-seven novel chalcone derivatives were designed and synthesized as neuraminidase(NA) inhibitors. A concise suitable synthetic strategy was employed in the target compounds’ synthesis with relatively high yields. The synthesized compounds were evaluated for their inhibitory activities against the NA of influenza A virus in vitro. The results show that compound 9b possesses the most potent NA inhibitory activity. Structure-activity relationship studies indicate that the chalcone system and hydrogen bond donor substituent are significant for the NA inhibitory activity. And the chalcone derivatives containing pyran ring have better NA inhibitory activity than those without the pyran ring. In addition, molecular docking studies reveal that compounds 9b and 9u are in the good binding mode with Zanamivir binding sites. This study indicates that compound 9b could be selected as a potent compound for further structural optimization and development of novel NA inhibitors.

Keywords

Chalcone derivative / Neuraminidase inhibitor / Molecular docking

References

[1] ZhuQ., BangT. H., OhnukiK., SawaiT., SawaiK., ShimizuaK.Sci. Rep., 2015, 5: 13194.

[2] MillsC. E., RobinsJ. M., LipsitchM.Nature, 2004, 4327019904.

[3] WangY., LeiF., LiX. L., HeY., LiJ., QiuR., WuX. Y., HaiL., WuY.Chem. Res. Chinese Universities, 2015, 3169421

[4] SubbaraoK., JosephT.Nat. Rev. Immunol., 2007, 7: 267.

[5] De ClercqE.Nat. Rev. Drug Discov., 2006, 5121015.

[6] MosconaA.N. Engl. J. Med., 2009, 360: 953.

[7] LiuD., FanZ., JiangJ., WeiJ., XinJ.Chem. Res. Chinese Universities, 2013, 294706.

[8] SidwellR. W., SmeeD. F.Expert Opin. Investig. Drugs, 2002, 11: 859.

[9] PaleseP.Nat. Med., 2004, 101282.

[10] ShiF. Y., FangH., XuW. F.Chem. Res. Chinese Universities, 2016, 32128.

[11] GhedinE., SengamalayN. A., ShumwayM., ZaborskyJ., TaylorJ., LipmanD. J., FraserC. M., TaubenbergerJ. K., SalzbergS. L.Nature, 2005, 437: 1162.

[12] ChenB., WangY., GuoH., ZengG.Eur. J. Med. Chem., 2016, 109: 199.

[13] NewmanD. J., CraggG. M.J. Nat. Prod., 2016, 793629.

[14] CraggG. M., NewmanD. J.BBA-Gen. Subjects, 2013, 183063670.

[15] NewmanD. J., CraggG. M.J. Nat. Prod., 2012, 753311.

[16] LiuA., WangH., LeeS. M., WangY., DuG.Bioorg. Med. Chem., 2008, 16: 7141.

[17] ParkJ. Y., JeongH. J., KimY. M., ParkS. J., RhoM. C., ParkK. H., RyuY. B., LeeW. S.Bioorg. Med. Chem. Lett., 2011, 21: 5602.

[18] RyuY. B., KimJ. H., ParkS. J., ChangJ. S., RhoM. C., BaeK. H., ParkK. H., LeeW. S.Bioorg. Med. Chem. Lett., 2010, 203971.

[19] ZuM., YangF., ZhouW., LiuA., DuG., ZhengL.Antivir. Res., 2012, 943217.

[20] ZhangJ., WangQ., FangH., XuW., LiuA., DuG.J. Med. Chem., 2008, 1673839

[21] ZhaoH., HuangD., CaflischA.Chem. Med. Chem., 2012, 7: 1983.

[22] DeLano W. L., PyMOL, 2002, http://www.pymol.org

[23] WallaceA. C., LaskowskiR. A., ThorntonJ. M.Protein Eng., 1995, 8: 127.

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Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH