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A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth
The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055733/ https://www.ncbi.nlm.nih.gov/pubmed/24925080 http://dx.doi.org/10.1371/journal.pone.0099584 |
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author | Lang, Liwei Liu, Xiaoyu Li, Yan Zhou, Qing Xie, Ping Yan, Chunhong Chen, Xiaoguang |
author_facet | Lang, Liwei Liu, Xiaoyu Li, Yan Zhou, Qing Xie, Ping Yan, Chunhong Chen, Xiaoguang |
author_sort | Lang, Liwei |
collection | PubMed |
description | The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers. |
format | Online Article Text |
id | pubmed-4055733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40557332014-06-18 A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth Lang, Liwei Liu, Xiaoyu Li, Yan Zhou, Qing Xie, Ping Yan, Chunhong Chen, Xiaoguang PLoS One Research Article The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers. Public Library of Science 2014-06-12 /pmc/articles/PMC4055733/ /pubmed/24925080 http://dx.doi.org/10.1371/journal.pone.0099584 Text en © 2014 Lang 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lang, Liwei Liu, Xiaoyu Li, Yan Zhou, Qing Xie, Ping Yan, Chunhong Chen, Xiaoguang A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title | A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title_full | A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title_fullStr | A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title_full_unstemmed | A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title_short | A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth |
title_sort | synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and tumor growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055733/ https://www.ncbi.nlm.nih.gov/pubmed/24925080 http://dx.doi.org/10.1371/journal.pone.0099584 |
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