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Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones

A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin–Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1-(...

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Autores principales: Jang, Ye Jin, Achary, Raghavendra, Lee, Hye Won, Lee, Hyo Jin, Lee, Chong-Kyo, Han, Soo Bong, Jung, Young-Sik, Kang, Nam Sook, Kim, Pilho, Kim, Meehyein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113773/
https://www.ncbi.nlm.nih.gov/pubmed/24794525
http://dx.doi.org/10.1016/j.antiviral.2014.04.013
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author Jang, Ye Jin
Achary, Raghavendra
Lee, Hye Won
Lee, Hyo Jin
Lee, Chong-Kyo
Han, Soo Bong
Jung, Young-Sik
Kang, Nam Sook
Kim, Pilho
Kim, Meehyein
author_facet Jang, Ye Jin
Achary, Raghavendra
Lee, Hye Won
Lee, Hyo Jin
Lee, Chong-Kyo
Han, Soo Bong
Jung, Young-Sik
Kang, Nam Sook
Kim, Pilho
Kim, Meehyein
author_sort Jang, Ye Jin
collection PubMed
description A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin–Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1-((5-fluoro-1H-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one (15a) with half-maximal effective concentrations of 17.4–21.1 μM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900 μM. To investigate the structure–activity relationships, two dozens of the hit analogs were synthesized. Among them, 15g, 15j, 15q, 15s, 15t and 15x had anti-influenza viral activity comparable or superior to that of the initial hit. The anti-influenza viral compounds efficiently suppressed not only viral protein level of the infected cells but also production of viral progeny in the culture supernatants in a dose-dependent manner. Based on a mode-of-action study, they did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors.
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spelling pubmed-71137732020-04-02 Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones Jang, Ye Jin Achary, Raghavendra Lee, Hye Won Lee, Hyo Jin Lee, Chong-Kyo Han, Soo Bong Jung, Young-Sik Kang, Nam Sook Kim, Pilho Kim, Meehyein Antiviral Res Article A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin–Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1-((5-fluoro-1H-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one (15a) with half-maximal effective concentrations of 17.4–21.1 μM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900 μM. To investigate the structure–activity relationships, two dozens of the hit analogs were synthesized. Among them, 15g, 15j, 15q, 15s, 15t and 15x had anti-influenza viral activity comparable or superior to that of the initial hit. The anti-influenza viral compounds efficiently suppressed not only viral protein level of the infected cells but also production of viral progeny in the culture supernatants in a dose-dependent manner. Based on a mode-of-action study, they did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors. Elsevier B.V. 2014-07 2014-04-30 /pmc/articles/PMC7113773/ /pubmed/24794525 http://dx.doi.org/10.1016/j.antiviral.2014.04.013 Text en Copyright © 2014 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Jang, Ye Jin
Achary, Raghavendra
Lee, Hye Won
Lee, Hyo Jin
Lee, Chong-Kyo
Han, Soo Bong
Jung, Young-Sik
Kang, Nam Sook
Kim, Pilho
Kim, Meehyein
Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title_full Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title_fullStr Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title_full_unstemmed Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title_short Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
title_sort synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1h)-ones
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113773/
https://www.ncbi.nlm.nih.gov/pubmed/24794525
http://dx.doi.org/10.1016/j.antiviral.2014.04.013
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