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Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives

Chalcone, a common chemical scaffold of many naturally occurring compounds, has been widely used as an effective template for drug discovery due to its broad biological activities. In this study, a series of chalcone derivatives were designed and synthesized based on the hybridization of 1-(2,4,6-tr...

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Autores principales: Li, Tong, Li, Weiwei, Yang, Xianjing, Chen, Gong, Jin, Xiaobao, Chen, Weiqiang, Ye, Lianbao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845116/
https://www.ncbi.nlm.nih.gov/pubmed/36685294
http://dx.doi.org/10.1016/j.jsps.2022.11.006
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author Li, Tong
Li, Weiwei
Yang, Xianjing
Chen, Gong
Jin, Xiaobao
Chen, Weiqiang
Ye, Lianbao
author_facet Li, Tong
Li, Weiwei
Yang, Xianjing
Chen, Gong
Jin, Xiaobao
Chen, Weiqiang
Ye, Lianbao
author_sort Li, Tong
collection PubMed
description Chalcone, a common chemical scaffold of many naturally occurring compounds, has been widely used as an effective template for drug discovery due to its broad biological activities. In this study, a series of chalcone derivatives were designed and synthesized based on the hybridization of 1-(2,4,6-trimethoxyphenyl)butan-1-one with chalcone. Interestingly, most of the target compounds exhibited inhibitory effect of tumor cells in vitro. Especially, (E)-3-(5-bromopyridin-2-yl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (B3) revealed over 10-fold potency than 5-fluorocrail against the Hela and MCF-7 cells with IC(50) values of 3.204 and 3.849 μM respectively. Moreover, B3 displayed low toxicity on normal cells. Further experiments indicated that B3 effectively inhibited the proliferation and migration of tumor cells, and promoted their apoptosis. The calculation and prediction of ADME showed that the target compounds may have good pharmacokinetic properties and oral bioavailability. Reverse molecular docking suggested that the possible target of B3 is CDK1. Taken together, these results suggested that B3 appears to be a promising candidate that merits further attention in the development of anticancer drugs.
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spelling pubmed-98451162023-01-19 Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives Li, Tong Li, Weiwei Yang, Xianjing Chen, Gong Jin, Xiaobao Chen, Weiqiang Ye, Lianbao Saudi Pharm J Original Article Chalcone, a common chemical scaffold of many naturally occurring compounds, has been widely used as an effective template for drug discovery due to its broad biological activities. In this study, a series of chalcone derivatives were designed and synthesized based on the hybridization of 1-(2,4,6-trimethoxyphenyl)butan-1-one with chalcone. Interestingly, most of the target compounds exhibited inhibitory effect of tumor cells in vitro. Especially, (E)-3-(5-bromopyridin-2-yl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (B3) revealed over 10-fold potency than 5-fluorocrail against the Hela and MCF-7 cells with IC(50) values of 3.204 and 3.849 μM respectively. Moreover, B3 displayed low toxicity on normal cells. Further experiments indicated that B3 effectively inhibited the proliferation and migration of tumor cells, and promoted their apoptosis. The calculation and prediction of ADME showed that the target compounds may have good pharmacokinetic properties and oral bioavailability. Reverse molecular docking suggested that the possible target of B3 is CDK1. Taken together, these results suggested that B3 appears to be a promising candidate that merits further attention in the development of anticancer drugs. Elsevier 2023-01 2022-11-16 /pmc/articles/PMC9845116/ /pubmed/36685294 http://dx.doi.org/10.1016/j.jsps.2022.11.006 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Li, Tong
Li, Weiwei
Yang, Xianjing
Chen, Gong
Jin, Xiaobao
Chen, Weiqiang
Ye, Lianbao
Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title_full Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title_fullStr Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title_full_unstemmed Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title_short Design, Synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
title_sort design, synthesis, anticancer evaluation and in silico studies of 2,4,6-trimethoxychalcone derivatives
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845116/
https://www.ncbi.nlm.nih.gov/pubmed/36685294
http://dx.doi.org/10.1016/j.jsps.2022.11.006
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