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

Molecules

Yaping Hu¹  Hongxi Zhu¹  Yongshou Tian¹  Zaiqiang Lei¹  Hongqian Zhao¹  Binfeng Chen¹  Peng Quan² 

[1] Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China;School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China;

关键词: influenza;    neuraminidase inhibitors;    oseltamivir analogues;   

DOI  :  10.3390/molecules24112176

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown