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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))...

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Autores principales: Jin, Lu, Wang, Meng-Ling, Lv, Yao, Zeng, Xue-Yi, Chen, Chao, Ren, Hai, Luo, Heng, Pan, Wei-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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