2. Academic Validation
  3. Synthesis and Biological Evaluation of NH2-Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors

Synthesis and Biological Evaluation of NH2-Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors

  • Molecules. 2019 Jun 10;24(11):2176. doi: 10.3390/molecules24112176.
Yaping Hu 1,  Binfeng Chen 2,  Zaiqiang Lei 3,  Hongqian Zhao 4,  Hongxi Zhu 5,  Peng Quan 6,  Yongshou Tian 7
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. hyp910309@163.com.
  • 2 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. yh_cbf@163.com.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. ZaiqiangLei@126.com.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. zhaohongqian999@163.com.
  • 5 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. 13125557362@163.com.
  • 6 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. quanpeng81@163.com.
  • 7 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. tianys@syphu.edu.cn.
PMID: 31185617 DOI: 10.3390/molecules24112176
Abstract

A series of NH2-sulfonyl oseltamivir analogues were designed, synthesized, and their inhibitory activities against neuraminidase from H5N1 subtype evaluated. The results indicated that the IC50 value of compound 4a, an oseltamivir analogue via methyl sulfonylation of C5-NH2, was 3.50 μM. Molecular docking simulations suggested that 4a retained most of the interactions formed by oseltamivir carboxylate moieties and formed an additional hydrogen bond with the methylsulfonyl group. Meanwhile, 4a showed high stability towards human liver microsomes. More importantly, 4a without basic moieties is not a zwitterion as reported on the general structure of neuraminidase inhibitors. This research will provide valuable reference for the research of new types of neuraminidase inhibitors.

Keywords

influenza; neuraminidase inhibitors; oseltamivir analogues.

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