Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization

A library of new heteroaromatic ring-linked chalcone analogs were designed and synthesized of these, compound 7m with α-CH3 substitution and bearing a benzofuran ring, displaying the most potent activity, with IC50 values of 0.07–0.183 µM against three cancer cells. Its low cytotoxicity toward norma...

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Autores principales:	Moran Sun, Yuyang Wang, Minghua Yuan, Qing Zhao, Yixin Zhang, Yongfang Yao, Yongtao Duan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	microtubules zebrafish angiogenesis chalcone analogs anti-tumor Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/14feabf116f24afb8a804711e97a959e
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spelling	oai:doaj.org-article:14feabf116f24afb8a804711e97a959e2021-11-30T19:30:03ZAngiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization2296-264610.3389/fchem.2021.766201https://doaj.org/article/14feabf116f24afb8a804711e97a959e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fchem.2021.766201/fullhttps://doaj.org/toc/2296-2646A library of new heteroaromatic ring-linked chalcone analogs were designed and synthesized of these, compound 7m with α-CH3 substitution and bearing a benzofuran ring, displaying the most potent activity, with IC50 values of 0.07–0.183 µM against three cancer cells. Its low cytotoxicity toward normal human cells and strong potency on drug-resistant cells revealed the possibility for cancer therapy. It also could moderately inhibit in vitro tubulin polymerization with an IC50 value of 12.23 µM, and the disruption of cellular architecture in MCF-7 cells was observed by an immunofluorescence assay. Cellular-based mechanism studies elucidated that 7m arrested the cell cycle at the G2/M phase and induced apoptosis by regulating the expression levels of caspases and PARP protein. Importantly, the compound 7 m was found to inhibit HUVEC tube formation, migration, and invasion in vitro. In vivo assay showed that 7m could effectively destroy angiogenesis of zebrafish embryos. Furthermore, our data suggested that treatment with 7m significantly reduced MCF-7 cell metastasis and proliferation in vitro and in zebrafish xenograft. Collectively, this work showed that chalcone hybrid 7m deserves further investigation as dual potential tubulin polymerization and angiogenesis inhibitor.Moran SunMoran SunYuyang WangMinghua YuanQing ZhaoYixin ZhangYongfang YaoYongtao DuanYongtao DuanFrontiers Media S.A.articlemicrotubuleszebrafishangiogenesischalcone analogsanti-tumorChemistryQD1-999ENFrontiers in Chemistry, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microtubules zebrafish angiogenesis chalcone analogs anti-tumor Chemistry QD1-999
spellingShingle	microtubules zebrafish angiogenesis chalcone analogs anti-tumor Chemistry QD1-999 Moran Sun Moran Sun Yuyang Wang Minghua Yuan Qing Zhao Yixin Zhang Yongfang Yao Yongtao Duan Yongtao Duan Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
description	A library of new heteroaromatic ring-linked chalcone analogs were designed and synthesized of these, compound 7m with α-CH3 substitution and bearing a benzofuran ring, displaying the most potent activity, with IC50 values of 0.07–0.183 µM against three cancer cells. Its low cytotoxicity toward normal human cells and strong potency on drug-resistant cells revealed the possibility for cancer therapy. It also could moderately inhibit in vitro tubulin polymerization with an IC50 value of 12.23 µM, and the disruption of cellular architecture in MCF-7 cells was observed by an immunofluorescence assay. Cellular-based mechanism studies elucidated that 7m arrested the cell cycle at the G2/M phase and induced apoptosis by regulating the expression levels of caspases and PARP protein. Importantly, the compound 7 m was found to inhibit HUVEC tube formation, migration, and invasion in vitro. In vivo assay showed that 7m could effectively destroy angiogenesis of zebrafish embryos. Furthermore, our data suggested that treatment with 7m significantly reduced MCF-7 cell metastasis and proliferation in vitro and in zebrafish xenograft. Collectively, this work showed that chalcone hybrid 7m deserves further investigation as dual potential tubulin polymerization and angiogenesis inhibitor.
format	article
author	Moran Sun Moran Sun Yuyang Wang Minghua Yuan Qing Zhao Yixin Zhang Yongfang Yao Yongtao Duan Yongtao Duan
author_facet	Moran Sun Moran Sun Yuyang Wang Minghua Yuan Qing Zhao Yixin Zhang Yongfang Yao Yongtao Duan Yongtao Duan
author_sort	Moran Sun
title	Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
title_short	Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
title_full	Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
title_fullStr	Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
title_full_unstemmed	Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
title_sort	angiogenesis, anti-tumor, and anti-metastatic activity of novel α-substituted hetero-aromatic chalcone hybrids as inhibitors of microtubule polymerization
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/14feabf116f24afb8a804711e97a959e
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Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization

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