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Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis
Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to β-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stabili...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448362/ https://www.ncbi.nlm.nih.gov/pubmed/36039017 http://dx.doi.org/10.1080/14756366.2022.2116015 |
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author | Wei, Tao Zheng, Zhiwei Wei, Xiaoyan Liu, Yugang Li, Wentao Fang, Bingqing Yun, Di Dong, Zhaojun Yi, Baozhu Li, Wulan Wu, Xiaoping Chen, Dezhi Chen, Liping Wu, Jianzhang |
author_facet | Wei, Tao Zheng, Zhiwei Wei, Xiaoyan Liu, Yugang Li, Wentao Fang, Bingqing Yun, Di Dong, Zhaojun Yi, Baozhu Li, Wulan Wu, Xiaoping Chen, Dezhi Chen, Liping Wu, Jianzhang |
author_sort | Wei, Tao |
collection | PubMed |
description | Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to β-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics. |
format | Online Article Text |
id | pubmed-9448362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-94483622022-09-07 Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis Wei, Tao Zheng, Zhiwei Wei, Xiaoyan Liu, Yugang Li, Wentao Fang, Bingqing Yun, Di Dong, Zhaojun Yi, Baozhu Li, Wulan Wu, Xiaoping Chen, Dezhi Chen, Liping Wu, Jianzhang J Enzyme Inhib Med Chem Research Paper Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to β-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics. Taylor & Francis 2022-08-29 /pmc/articles/PMC9448362/ /pubmed/36039017 http://dx.doi.org/10.1080/14756366.2022.2116015 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://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/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Wei, Tao Zheng, Zhiwei Wei, Xiaoyan Liu, Yugang Li, Wentao Fang, Bingqing Yun, Di Dong, Zhaojun Yi, Baozhu Li, Wulan Wu, Xiaoping Chen, Dezhi Chen, Liping Wu, Jianzhang Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title | Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title_full | Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title_fullStr | Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title_full_unstemmed | Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title_short | Rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ROS and ER stress mediated cell apoptosis and pyroptosis |
title_sort | rational design, synthesis, and pharmacological characterisation of dicarbonyl curcuminoid analogues with improved stability against lung cancer via ros and er stress mediated cell apoptosis and pyroptosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448362/ https://www.ncbi.nlm.nih.gov/pubmed/36039017 http://dx.doi.org/10.1080/14756366.2022.2116015 |
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