Synthesis and Biological Evaluation of <i>NH</i><sub>2</sub>-Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors
Yaping Hu,
Binfeng Chen,
Zaiqiang Lei,
Hongqian Zhao,
Hongxi Zhu,
Peng Quan,
Yongshou Tian
Affiliations
Yaping Hu
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Binfeng Chen
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Zaiqiang Lei
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Hongqian Zhao
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Hongxi Zhu
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Peng Quan
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
Yongshou Tian
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
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.
