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Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety
Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC(50) values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160875/ https://www.ncbi.nlm.nih.gov/pubmed/34065165 http://dx.doi.org/10.3390/molecules26103041 |
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author | Hu, Xiaohan Tang, Sheng Yang, Feiyi Zheng, Pengwu Xu, Shan Pan, Qingshan Zhu, Wufu |
author_facet | Hu, Xiaohan Tang, Sheng Yang, Feiyi Zheng, Pengwu Xu, Shan Pan, Qingshan Zhu, Wufu |
author_sort | Hu, Xiaohan |
collection | PubMed |
description | Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC(50) values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents. |
format | Online Article Text |
id | pubmed-8160875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81608752021-05-29 Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety Hu, Xiaohan Tang, Sheng Yang, Feiyi Zheng, Pengwu Xu, Shan Pan, Qingshan Zhu, Wufu Molecules Article Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC(50) values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents. MDPI 2021-05-20 /pmc/articles/PMC8160875/ /pubmed/34065165 http://dx.doi.org/10.3390/molecules26103041 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hu, Xiaohan Tang, Sheng Yang, Feiyi Zheng, Pengwu Xu, Shan Pan, Qingshan Zhu, Wufu Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title | Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title_full | Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title_fullStr | Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title_full_unstemmed | Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title_short | Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety |
title_sort | design, synthesis, and antitumor activity of olmutinib derivatives containing acrylamide moiety |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160875/ https://www.ncbi.nlm.nih.gov/pubmed/34065165 http://dx.doi.org/10.3390/molecules26103041 |
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