tetano
Editor, Senior Moderator
Bioorg Med Chem. 2019 Oct 15:115147. doi: 10.1016/j.bmc.2019.115147. [Epub ahead of print] [h=1]Design, synthesis and biological evaluation of amino acids-oleanolic acid conjugates as influenza virus inhibitors.[/h]
Meng L[SUP]1[/SUP], Su Y[SUP]1[/SUP], Yang F[SUP]1[/SUP], Xiao S[SUP]2[/SUP], Yin Z[SUP]1[/SUP], Liu J[SUP]1[/SUP], Zhong J[SUP]3[/SUP], Zhou D[SUP]2[/SUP], Yu F[SUP]4[/SUP].
[h=3]Author information[/h] 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 Faculty of Life Science and Technology of Kunming University of Science and Technology, Kunming, Yunnan 650500, China. 4 Medical School of Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: feiyuz8@kmust.edu.cn.
[h=3]Abstract[/h] Viral entry inhibitors are of great importance in current efforts to develop a new generation of anti-influenza drugs. Inspired by the discovery of a series of pentacyclic triterpene derivatives as entry inhibitors targeting the HA protein of influenza virus, we designed and synthesized 32 oleanolic acid (OA) analogues in this study by conjugating different amino acids to the 28-COOH of OA. The antiviral activity of these compounds was evaluated in vitro. Some of these compounds revealed impressive anti-influenza potencies against influenza A/WSN/33 (H1N1) virus. Among them, compound 15a exhibited robust potency and broad antiviral spectrum with IC[SUB]50[/SUB] values at the low-micromolar level against four different influenza strains. Hemagglutination inhibition (HI) assay and docking experiment indicated that these OA analogues may act in the same way as their parent compound by interrupting the interaction between HA protein of influenza virus and the host cell sialic acid receptor via binding to HA, thus blocking viral entry.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amino acids; Entry inhibitor; Hemagglutinin; Influenza A virus; Oleanolic acid
PMID: 31635892 DOI: 10.1016/j.bmc.2019.115147
Meng L[SUP]1[/SUP], Su Y[SUP]1[/SUP], Yang F[SUP]1[/SUP], Xiao S[SUP]2[/SUP], Yin Z[SUP]1[/SUP], Liu J[SUP]1[/SUP], Zhong J[SUP]3[/SUP], Zhou D[SUP]2[/SUP], Yu F[SUP]4[/SUP].
[h=3]Author information[/h] 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 Faculty of Life Science and Technology of Kunming University of Science and Technology, Kunming, Yunnan 650500, China. 4 Medical School of Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: feiyuz8@kmust.edu.cn.
[h=3]Abstract[/h] Viral entry inhibitors are of great importance in current efforts to develop a new generation of anti-influenza drugs. Inspired by the discovery of a series of pentacyclic triterpene derivatives as entry inhibitors targeting the HA protein of influenza virus, we designed and synthesized 32 oleanolic acid (OA) analogues in this study by conjugating different amino acids to the 28-COOH of OA. The antiviral activity of these compounds was evaluated in vitro. Some of these compounds revealed impressive anti-influenza potencies against influenza A/WSN/33 (H1N1) virus. Among them, compound 15a exhibited robust potency and broad antiviral spectrum with IC[SUB]50[/SUB] values at the low-micromolar level against four different influenza strains. Hemagglutination inhibition (HI) assay and docking experiment indicated that these OA analogues may act in the same way as their parent compound by interrupting the interaction between HA protein of influenza virus and the host cell sialic acid receptor via binding to HA, thus blocking viral entry.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Amino acids; Entry inhibitor; Hemagglutinin; Influenza A virus; Oleanolic acid
PMID: 31635892 DOI: 10.1016/j.bmc.2019.115147