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Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity
Chromone has emerged as one of the most important synthetic scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and synthesised, in order to discover promising anti...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725944/ https://www.ncbi.nlm.nih.gov/pubmed/34957906 http://dx.doi.org/10.1080/14756366.2021.2018685 |
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author | Sun, Jianan Mu, Jiahui Wang, Shenglin Jia, Cai Li, Dahong Hua, Huiming Cao, Hao |
author_facet | Sun, Jianan Mu, Jiahui Wang, Shenglin Jia, Cai Li, Dahong Hua, Huiming Cao, Hao |
author_sort | Sun, Jianan |
collection | PubMed |
description | Chromone has emerged as one of the most important synthetic scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and synthesised, in order to discover promising anti-breast tumour candidates. Almost all target derivatives showed antiproliferative activity against MCF-7 and MDA-MB-231 cell lines. In particular, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed the most potent antiproliferative activity with IC(50) values of 1.83 and 1.90 μM, respectively, and it also exhibited certain selectivity between tumour cells and normal cells. Further mechanism exploration against MDA-MB-231 cells showed that it possibly induced G2/M phase arrest and apoptosis by generating intracellular ROS and activating DNA damage. In addition, it also inhibited MDA-MB-231 cells metastasis, invasion and adhesion. Overall, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed potent antitumor activities and relatively low side effects, and deserved further investigation. |
format | Online Article Text |
id | pubmed-8725944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-87259442022-01-05 Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity Sun, Jianan Mu, Jiahui Wang, Shenglin Jia, Cai Li, Dahong Hua, Huiming Cao, Hao J Enzyme Inhib Med Chem Short Communication Chromone has emerged as one of the most important synthetic scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and synthesised, in order to discover promising anti-breast tumour candidates. Almost all target derivatives showed antiproliferative activity against MCF-7 and MDA-MB-231 cell lines. In particular, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed the most potent antiproliferative activity with IC(50) values of 1.83 and 1.90 μM, respectively, and it also exhibited certain selectivity between tumour cells and normal cells. Further mechanism exploration against MDA-MB-231 cells showed that it possibly induced G2/M phase arrest and apoptosis by generating intracellular ROS and activating DNA damage. In addition, it also inhibited MDA-MB-231 cells metastasis, invasion and adhesion. Overall, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed potent antitumor activities and relatively low side effects, and deserved further investigation. Taylor & Francis 2021-12-27 /pmc/articles/PMC8725944/ /pubmed/34957906 http://dx.doi.org/10.1080/14756366.2021.2018685 Text en © 2021 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 | Short Communication Sun, Jianan Mu, Jiahui Wang, Shenglin Jia, Cai Li, Dahong Hua, Huiming Cao, Hao Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title | Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title_full | Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title_fullStr | Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title_full_unstemmed | Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title_short | Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
title_sort | design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725944/ https://www.ncbi.nlm.nih.gov/pubmed/34957906 http://dx.doi.org/10.1080/14756366.2021.2018685 |
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