Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression

A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of comp...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Lintao, Yang, Yuting, Wang, Zhijun, Wu, Xi, Su, Feng, Li, Mengyao, Jing, Xiaobi, Han, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179225/
https://www.ncbi.nlm.nih.gov/pubmed/32150865
http://dx.doi.org/10.3390/molecules25051162
_version_ 1783525625590448128
author Wu, Lintao
Yang, Yuting
Wang, Zhijun
Wu, Xi
Su, Feng
Li, Mengyao
Jing, Xiaobi
Han, Chun
author_facet Wu, Lintao
Yang, Yuting
Wang, Zhijun
Wu, Xi
Su, Feng
Li, Mengyao
Jing, Xiaobi
Han, Chun
author_sort Wu, Lintao
collection PubMed
description A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53(−/−)) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.
format Online
Article
Text
id pubmed-7179225
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71792252020-04-28 Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression Wu, Lintao Yang, Yuting Wang, Zhijun Wu, Xi Su, Feng Li, Mengyao Jing, Xiaobi Han, Chun Molecules Article A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53(−/−)) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction. MDPI 2020-03-05 /pmc/articles/PMC7179225/ /pubmed/32150865 http://dx.doi.org/10.3390/molecules25051162 Text en © 2020 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
Wu, Lintao
Yang, Yuting
Wang, Zhijun
Wu, Xi
Su, Feng
Li, Mengyao
Jing, Xiaobi
Han, Chun
Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title_full Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title_fullStr Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title_full_unstemmed Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title_short Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression
title_sort design, synthesis, and biological evaluation of aromatic amide-substituted benzimidazole-derived chalcones. the effect of upregulating tp53 protein expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179225/
https://www.ncbi.nlm.nih.gov/pubmed/32150865
http://dx.doi.org/10.3390/molecules25051162
work_keys_str_mv AT wulintao designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT yangyuting designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT wangzhijun designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT wuxi designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT sufeng designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT limengyao designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT jingxiaobi designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression
AT hanchun designsynthesisandbiologicalevaluationofaromaticamidesubstitutedbenzimidazolederivedchalconestheeffectofupregulatingtp53proteinexpression

Ejemplares similares