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Structure-activity relationship studies of 1-(1'-hydroxyalkyl)rupestonic acid methyl esters against influenza viruses

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  • Structure-activity relationship studies of 1-(1'-hydroxyalkyl)rupestonic acid methyl esters against influenza viruses

    Bioorg Med Chem Lett. 2016 Jun 6. pii: S0960-894X(16)30622-9. doi: 10.1016/j.bmcl.2016.06.011. [Epub ahead of print]
    Structure-activity relationship studies of 1-(1'-hydroxyalkyl)rupestonic acid methyl esters against influenza viruses.

    Li G1, Zhao JY2, Niu C2, Nie LF2, Dong CZ3, Aisa HA4.
    Author information

    Abstract

    A series of 1-(1'-hydroxyalkyl)rupestonic acid methyl esters were synthesized via the condensation of methyl rupestonate with various aldehydes in the presence of LDA. This mixed aldol reaction was highly stereoselective and all the new compounds were elucidated by detailed NMR and MS analyses. The absolute configurations of the newly formed stereocenters were further confirmed by X-ray crystallographic analysis of 3d, the results of which were found to be opposite to the prediction based on Zimmerman-Traxler's and Houk's models. All the compounds synthesized were then evaluated for their in vitro inhibitory activities against influenza A (H1N1 and H3N2) and B viruses. The data showed that 3p displayed the highest activity against influenza A H1N1 (IC50=0.69μg/mL) and H3N2 (IC50=0.69μg/mL) viruses, which were even better than Ribavirin and Oseltmivir. On the other hand, both 3c and 3o were found to show comparable activities with the reference drugs in inhibiting both influenza A and B viruses. Further studies will focus on reducing the cytotoxicity of the hits reported in this work.
    Copyright ? 2016 Elsevier Ltd. All rights reserved.


    KEYWORDS:

    Anti-influenza viruses; Rupestonic acid; Synthesis; X-ray crystallographic analysis

    PMID: 28196702 DOI: 10.1016/j.bmcl.2016.06.011
    [PubMed - as supplied by publisher]
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