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Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D

Novel antiviral agents for influenza, which poses a substantial threat to humans, are required. Cyclobakuchiols A and B have been isolated from Psoralea glandulosa, and cyclobakuchiol C has been isolated from P. corylifolia. The structural differences between cyclobakuchiol A and C arise due to the...

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Autores principales: Shoji, Masaki, Esumi, Tomoyuki, Tanaka, Narue, Takeuchi, Misa, Yamaji, Saki, Watanabe, Mihiro, Takahashi, Etsuhisa, Kido, Hiroshi, Yamamoto, Masayuki, Kuzuhara, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997032/
https://www.ncbi.nlm.nih.gov/pubmed/33770117
http://dx.doi.org/10.1371/journal.pone.0248960
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author Shoji, Masaki
Esumi, Tomoyuki
Tanaka, Narue
Takeuchi, Misa
Yamaji, Saki
Watanabe, Mihiro
Takahashi, Etsuhisa
Kido, Hiroshi
Yamamoto, Masayuki
Kuzuhara, Takashi
author_facet Shoji, Masaki
Esumi, Tomoyuki
Tanaka, Narue
Takeuchi, Misa
Yamaji, Saki
Watanabe, Mihiro
Takahashi, Etsuhisa
Kido, Hiroshi
Yamamoto, Masayuki
Kuzuhara, Takashi
author_sort Shoji, Masaki
collection PubMed
description Novel antiviral agents for influenza, which poses a substantial threat to humans, are required. Cyclobakuchiols A and B have been isolated from Psoralea glandulosa, and cyclobakuchiol C has been isolated from P. corylifolia. The structural differences between cyclobakuchiol A and C arise due to the oxidation state of isopropyl group, and these compounds can be derived from (+)-(S)-bakuchiol, a phenolic isoprenoid compound present in P. corylifolia seeds. We previously reported that bakuchiol induces enantiospecific anti-influenza A virus activity involving nuclear factor erythroid 2-related factor 2 (Nrf2) activation. However, it remains unclear whether cyclobakuchiols A–C induce anti-influenza A virus activity. In this study, cyclobakuchiols A, B, and C along with cyclobakuchiol D, a new artificial compound derived from cyclobakuchiol B, were synthesized and examined for their anti-influenza A virus activities using Madin-Darby canine kidney cells. As a result, cyclobakuchiols A–D were found to inhibit influenza A viral infection, growth, and the reduction of expression of viral mRNAs and proteins in influenza A virus-infected cells. Additionally, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. In addition, cyclobakuchiols A–D upregulated the mRNA levels of NAD(P)H quinone oxidoreductase 1, an Nrf2-induced gene, in influenza A virus-infected cells. Notably, cyclobakuchiols A, B, and C, but not D, induced the Nrf2 activation pathway. These findings demonstrate that cyclobakuchiols have anti-influenza viral activity involving host cell oxidative stress response. In addition, our results suggest that the suitably spatial configuration between oxidized isopropyl group and phenol moiety in the structure of cyclobakuchiols is required for their effect.
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spelling pubmed-79970322021-04-06 Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D Shoji, Masaki Esumi, Tomoyuki Tanaka, Narue Takeuchi, Misa Yamaji, Saki Watanabe, Mihiro Takahashi, Etsuhisa Kido, Hiroshi Yamamoto, Masayuki Kuzuhara, Takashi PLoS One Research Article Novel antiviral agents for influenza, which poses a substantial threat to humans, are required. Cyclobakuchiols A and B have been isolated from Psoralea glandulosa, and cyclobakuchiol C has been isolated from P. corylifolia. The structural differences between cyclobakuchiol A and C arise due to the oxidation state of isopropyl group, and these compounds can be derived from (+)-(S)-bakuchiol, a phenolic isoprenoid compound present in P. corylifolia seeds. We previously reported that bakuchiol induces enantiospecific anti-influenza A virus activity involving nuclear factor erythroid 2-related factor 2 (Nrf2) activation. However, it remains unclear whether cyclobakuchiols A–C induce anti-influenza A virus activity. In this study, cyclobakuchiols A, B, and C along with cyclobakuchiol D, a new artificial compound derived from cyclobakuchiol B, were synthesized and examined for their anti-influenza A virus activities using Madin-Darby canine kidney cells. As a result, cyclobakuchiols A–D were found to inhibit influenza A viral infection, growth, and the reduction of expression of viral mRNAs and proteins in influenza A virus-infected cells. Additionally, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. In addition, cyclobakuchiols A–D upregulated the mRNA levels of NAD(P)H quinone oxidoreductase 1, an Nrf2-induced gene, in influenza A virus-infected cells. Notably, cyclobakuchiols A, B, and C, but not D, induced the Nrf2 activation pathway. These findings demonstrate that cyclobakuchiols have anti-influenza viral activity involving host cell oxidative stress response. In addition, our results suggest that the suitably spatial configuration between oxidized isopropyl group and phenol moiety in the structure of cyclobakuchiols is required for their effect. Public Library of Science 2021-03-26 /pmc/articles/PMC7997032/ /pubmed/33770117 http://dx.doi.org/10.1371/journal.pone.0248960 Text en © 2021 Shoji et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shoji, Masaki
Esumi, Tomoyuki
Tanaka, Narue
Takeuchi, Misa
Yamaji, Saki
Watanabe, Mihiro
Takahashi, Etsuhisa
Kido, Hiroshi
Yamamoto, Masayuki
Kuzuhara, Takashi
Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title_full Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title_fullStr Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title_full_unstemmed Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title_short Organic synthesis and anti-influenza A virus activity of cyclobakuchiols A, B, C, and D
title_sort organic synthesis and anti-influenza a virus activity of cyclobakuchiols a, b, c, and d
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997032/
https://www.ncbi.nlm.nih.gov/pubmed/33770117
http://dx.doi.org/10.1371/journal.pone.0248960
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