标题:Discovery of novel “Dual-site” binding oseltamivir derivatives as potent influenza virus neuraminidase inhibitors
作者:Ai W.; Zhang J.; Zalloum W.A.; Jia R.; Cherukupalli S.; Ding X.; Sun Z.; Sun L.;等 更多
作者机构:[Ai, W] The Second Hospital of Shandong University, No. 247 Beiyuan Avenue, Jinan, Shandong 250033, China;[ Zhang, J] The Second Hospital of Shandong 更多
通讯作者:Zhan, P(zhanpeng1982@sdu.edu.cn)
通讯作者地址:[Zhan, P] Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong U 更多
来源:European Journal of Medicinal Chemistry
出版年:2020
卷:191
DOI:10.1016/j.ejmech.2020.112147
关键词:150-cavity; Active site; Influenza virus; Neuraminidase inhibitors; Oseltamivir derivatives
摘要:From our research group, it was noticed that oseltamivir derivatives targeting 150-cavity of neuraminidase enzyme (NA) could significantly increase antiviral activity. Thus, we further enriched the C5–NH2 position of oseltamivir structure to obtain more potent oseltamivir derivatives. In this article a series of oseltamivir derivatives were synthesized by modifying C5–NH2 position of oseltamivir. All the compounds were evaluated for in vitro antiviral activity against H5N1 and H5N8. Encouragingly, compounds 9a and 11e were exhibited prominent activity, which is similar to oseltamivir carboxylate (OSC) and in NAs inhibitory assay, 11e showed remarkable potency against N1 (H5N1), N2 (H5N2), N6 (H5N6) and N8 (H5N8). In addition, 11e demonstrated low cytotoxicity and no obvious toxicity at the dose of 1500 mg/kg in mice. Molecular docking studies of 9a and 11e provided a plausible rationale for the high potency against group-1 NAs. This work provided new insights to design further neuraminidase inhibitors, which can help to investigate new potent inhibitors for group-1 and group-2 shortly. © 2020 Elsevier Masson SAS
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079587645&doi=10.1016%2fj.ejmech.2020.112147&partnerID=40&md5=7e840ae63831a92ecde6c08ed70e59e5
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