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Eur J Med Chem. 2019 Aug 13;182:111622. doi: 10.1016/j.ejmech.2019.111622. [Epub ahead of print]
Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity.
Su Y1, Meng L1, Sun J2, Li W1, Shao L1, Chen K1, Zhou D2, Yang F3, Yu F4.
Author information
1 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. 3 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. Electronic address: yangfan@kmust.edu.cn. 4 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. Electronic address: feiyuz8@kmust.edu.cn.
Abstract
The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47 μM, and no obvious cytotoxic effect on MDCK cells was observed at 100 μM. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Entry inhibitor; Hemagglutinin; Influenza virus; Oleanolic acid
PMID: 31425909 DOI: 10.1016/j.ejmech.2019.111622
Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity.
Su Y1, Meng L1, Sun J2, Li W1, Shao L1, Chen K1, Zhou D2, Yang F3, Yu F4.
Author information
1 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. 3 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. Electronic address: yangfan@kmust.edu.cn. 4 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. Electronic address: feiyuz8@kmust.edu.cn.
Abstract
The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47 μM, and no obvious cytotoxic effect on MDCK cells was observed at 100 μM. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Entry inhibitor; Hemagglutinin; Influenza virus; Oleanolic acid
PMID: 31425909 DOI: 10.1016/j.ejmech.2019.111622