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Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro
Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp(2))...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539111/ https://www.ncbi.nlm.nih.gov/pubmed/31064088 http://dx.doi.org/10.3390/molecules24091749 |
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author | Jin, Lu Wang, Meng-Ling Lv, Yao Zeng, Xue-Yi Chen, Chao Ren, Hai Luo, Heng Pan, Wei-Dong |
author_facet | Jin, Lu Wang, Meng-Ling Lv, Yao Zeng, Xue-Yi Chen, Chao Ren, Hai Luo, Heng Pan, Wei-Dong |
author_sort | Jin, Lu |
collection | PubMed |
description | Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp(2))-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure–activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates. |
format | Online Article Text |
id | pubmed-6539111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65391112019-05-31 Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro Jin, Lu Wang, Meng-Ling Lv, Yao Zeng, Xue-Yi Chen, Chao Ren, Hai Luo, Heng Pan, Wei-Dong Molecules Article Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp(2))-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure–activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates. MDPI 2019-05-06 /pmc/articles/PMC6539111/ /pubmed/31064088 http://dx.doi.org/10.3390/molecules24091749 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jin, Lu Wang, Meng-Ling Lv, Yao Zeng, Xue-Yi Chen, Chao Ren, Hai Luo, Heng Pan, Wei-Dong Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title | Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title_full | Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title_fullStr | Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title_full_unstemmed | Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title_short | Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro |
title_sort | design and synthesis of flavonoidal ethers and their anti-cancer activity in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539111/ https://www.ncbi.nlm.nih.gov/pubmed/31064088 http://dx.doi.org/10.3390/molecules24091749 |
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