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Design and one-pot synthesis of 2-thiazolylhydrazone derivatives as influenza neuraminidase inhibitors

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Abstract

Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives, \(\alpha \)-haloketones and thiosemicarbazide. The structures of compounds 1 and 2 were characterized by \(^{1}\hbox {H}\) NMR and \(^{13}\hbox {C}\) NMR, and compound 1g was further confirmed by X-ray crystallography. All of the target compounds were evaluated for their NA inhibitory activity against influenza viral neuraminidase (H1N1) in vitro, and the results showed that many compounds exhibited moderate to strong inhibitory activities against influenza viral neuraminidase (H1N1). Among them, compounds 1p, 1q and 2c showed the most potent inhibitory activities with \(\hbox {IC}_{50}\) values ranging from 10.50 to \(13.75\, \upmu \hbox {g}/\hbox {mL}\). Our structure–activity relationship analysis indicated that 2-thiazolylhydrazone is an effective scaffold for NA inhibitors and that introducing an ethoxycarbonyl group to the 5-position of thiazole ring could enhance inhibitory potency. Molecular docking was performed on the most active compounds 1p and 2c to provide more insight into their mechanism of interaction.

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Acknowledgements

This work was supported by Emergency Project of National Natural Science Fund (No. 21442014). The institute of Materia Medica of Chinese Academy of Medical Sciences and Peking Union Medical College provided the biological activity assays.

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China

    Keyang Yuan, Mengwu Xiao, Ying Tan, Jiao Ye, Yongle Xie, Xiaoxiao Sun & Aixi Hu

  2. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Wenwen Lian & Ailin Liu

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  1. Keyang Yuan
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  2. Mengwu Xiao
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Correspondence to Jiao Ye or Aixi Hu.

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Yuan, K., Xiao, M., Tan, Y. et al. Design and one-pot synthesis of 2-thiazolylhydrazone derivatives as influenza neuraminidase inhibitors. Mol Divers 21, 565–576 (2017). https://doi.org/10.1007/s11030-017-9740-0

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  • DOI: https://doi.org/10.1007/s11030-017-9740-0

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