• Novel synthetic process for the core str

    From ScienceDaily@1:317/3 to All on Wed Feb 9 21:30:36 2022
    Novel synthetic process for the core structure of the fungal antiviral
    agent neoechinulin B and its derivatives

    Date:
    February 9, 2022
    Source:
    Tokyo University of Science
    Summary:
    The fungus-derived compound neoechinulin B demonstrates promising
    antiviral activity. To realize its potential as an antiviral agent,
    however, a viable method for preparing more potent derivatives
    synthetically is necessary. In a recent breakthrough, scientists
    from Japan designed a simple route for synthesizing neoechinulin B
    and its derivatives under mild laboratory conditions. Neoechinulin
    B and six derivatives exhibited excellent antiviral activities
    against hepatitis C virus and SARS-CoV-2, the virus responsible
    for the COVID-19 pandemic.



    FULL STORY ==========================================================================
    The solutions to many of humanity's problems can be found within
    nature. For instance, who could have guessed that an antibiotic as
    powerful as penicillin would be found in a common mold, or that the drug aspirin would be derived from the bark of the willow tree?

    ========================================================================== Research into natural products has become a crucial part of drug
    discovery.

    Natural products have exhibited promising specificity and efficacy when
    used against a variety of pathogens, including viruses. For instance, an organic compound called neoechinulin B, isolated from the fungus Eurotium rubrum,has demonstrated antiviral activity against hepatitis C virus
    (HCV). However, the isolation of such compounds from natural sources
    can get quite tedious and expensive. Yet, the attempts to synthetically synthesize it seem to be very scarce.

    Thus, a group of scientists from across Japan rose to the occasion
    and embarked on a mission: To discover a simple route for synthesizing neoechinulin B under laboratory conditions. The team included Prof. Kouji Kuramochi and Dr. Koichi Watashi from Tokyo University of Science,
    along with Dr. Hirofumi Ohashi, Dr.

    Shusuke Tomoshige, Dr. Kenji Ohgane, and Dr. Shinji Kamisuki from the
    National Institute of Infectious Diseases, Tohoku University, Ochanomizu University, and Azabu University, respectively. Their findings were
    recently published in the Journal of Natural Products.

    Commenting on their strategy, Prof. Kuramochi, the lead author of the
    study, says: "We designed a streamlined two-step synthesis strategy to
    obtain diketopiperazine scaffold of neoechinulin B. The process involved
    the base- induced coupling of available piperazine-2,5-dione derivative
    was aldehydes.

    The coupled products were then treated with a commercial reagent called
    tetra- n-butylammonium fluoride (TBAF) which gave us neoechinulin
    B and its 16 other derivatives." To ascertain the efficacy of their
    products, the team tested the antiviral activity of neoechinulin B and its derivatives against different positive- strand RNA viruses, such as HCV
    and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They
    found that some derivatives showed anti-HCV activity with minimal cell toxicity, while others showed anti-SARS-CoV-2.

    Moreover, six derivatives exhibited both strong anti-HCV and SARS-CoV-2.

    Further studies by the research team uncovered that neoechinulin
    B and one derivative can reduced the transcriptional activity of
    liver X receptors (LXRs). This subsequently disrupts the formation of double-membrane vesicles (DMV), which are the sites where viral RNA
    replication occur. This process results in reduced viral replication in
    the infected cells.

    Along with the 17 active compounds, the scientists also produced
    three other compounds which, while structurally related to the others, possessed none of the antiviral properties. Further investigation into
    their molecular structure revealed that inactive compounds were missing
    the exomethylene moiety which is the key to the antiviral activities of neoechinulin B and its 16 derivatives against HCV and SARS-CoV-2.

    The team believes that the insights from this research could be used as a framework for the development of new broad-spectrum antiviral drugs. The
    study also solidifies the fact that natural products can act as promising
    lead compounds for the development of antiviral drugs. "The skeleton of neoechinulin B is simple, but only one chemical synthesis method has
    been reported in the past. Our research presented a simple and viable
    method for obtaining promising antiviral compounds bringing us one step
    closer to its practical application," concludes Prof. Kuramochi.

    ========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Kota Nishiuchi, Hirofumi Ohashi, Kazane Nishioka, Masako Yamasaki,
    Masateru Furuta, Takumi Mashiko, Shusuke Tomoshige,
    Kenji Ohgane, Shinji Kamisuki, Koichi Watashi, Kouji
    Kuramochi. Synthesis and Antiviral Activities of Neoechinulin B
    and Its Derivatives. Journal of Natural Products, 2021; 85 (1):
    284 DOI: 10.1021/acs.jnatprod.1c01120 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/02/220209112123.htm

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