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Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors
A series of novel 2-aryl-benzimidazole derivatives of dehydroabietic acid were synthesized and characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analyses. All the target compounds were evaluated for their in vitro cytotoxic activity against SMMC-7721, MDA-MB-231, HeLa and CT-26 cancer cell...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080489/ https://www.ncbi.nlm.nih.gov/pubmed/35539265 http://dx.doi.org/10.1039/c8ra02078g |
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author | Miao, Ting-Ting Tao, Xu-Bing Li, Dong-Dong Chen, Hao Jin, Xiao-Yan Geng, Yi Wang, Shi-Fa Gu, Wen |
author_facet | Miao, Ting-Ting Tao, Xu-Bing Li, Dong-Dong Chen, Hao Jin, Xiao-Yan Geng, Yi Wang, Shi-Fa Gu, Wen |
author_sort | Miao, Ting-Ting |
collection | PubMed |
description | A series of novel 2-aryl-benzimidazole derivatives of dehydroabietic acid were synthesized and characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analyses. All the target compounds were evaluated for their in vitro cytotoxic activity against SMMC-7721, MDA-MB-231, HeLa and CT-26 cancer cell lines and the normal hepatocyte cell line QSG-7701 through MTT assays. Among them, compound 6j displayed the most potent cytotoxic activity with IC(50) values of 0.08 ± 0.01, 0.19 ± 0.04, 0.23 ± 0.05 and 0.42 ± 0.07 μM, respectively, and substantially reduced cytotoxicity against QSG-7701 cells (5.82 ± 0.38 μM). The treatment of SMMC-7721 cells with compound 6j led to considerable inhibition of cell migration ability. The influence of compound 6j on cell cycle distribution was assessed on SMMC-7721 cells, exhibiting a cell cycle arrest at the G2/M phase. Moreover, tubulin polymerization assays and immunofluorescence assays elucidated that compound 6j could significantly inhibit tubulin polymerization and disrupt the intracellular microtubule network. A molecular docking study provided insight into the binding mode of compound 6j in the colchicine site of tubulin. In addition, compound 6j was found to induce apoptosis of SMMC-7721 cells, an increase of intracellular ROS level and a loss of mitochondrial membrane potential in a dose-dependent manner. These findings provided new molecular scaffolds for the further development of novel antitumor agents targeting tubulin polymerization. |
format | Online Article Text |
id | pubmed-9080489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90804892022-05-09 Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors Miao, Ting-Ting Tao, Xu-Bing Li, Dong-Dong Chen, Hao Jin, Xiao-Yan Geng, Yi Wang, Shi-Fa Gu, Wen RSC Adv Chemistry A series of novel 2-aryl-benzimidazole derivatives of dehydroabietic acid were synthesized and characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analyses. All the target compounds were evaluated for their in vitro cytotoxic activity against SMMC-7721, MDA-MB-231, HeLa and CT-26 cancer cell lines and the normal hepatocyte cell line QSG-7701 through MTT assays. Among them, compound 6j displayed the most potent cytotoxic activity with IC(50) values of 0.08 ± 0.01, 0.19 ± 0.04, 0.23 ± 0.05 and 0.42 ± 0.07 μM, respectively, and substantially reduced cytotoxicity against QSG-7701 cells (5.82 ± 0.38 μM). The treatment of SMMC-7721 cells with compound 6j led to considerable inhibition of cell migration ability. The influence of compound 6j on cell cycle distribution was assessed on SMMC-7721 cells, exhibiting a cell cycle arrest at the G2/M phase. Moreover, tubulin polymerization assays and immunofluorescence assays elucidated that compound 6j could significantly inhibit tubulin polymerization and disrupt the intracellular microtubule network. A molecular docking study provided insight into the binding mode of compound 6j in the colchicine site of tubulin. In addition, compound 6j was found to induce apoptosis of SMMC-7721 cells, an increase of intracellular ROS level and a loss of mitochondrial membrane potential in a dose-dependent manner. These findings provided new molecular scaffolds for the further development of novel antitumor agents targeting tubulin polymerization. The Royal Society of Chemistry 2018-05-16 /pmc/articles/PMC9080489/ /pubmed/35539265 http://dx.doi.org/10.1039/c8ra02078g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Miao, Ting-Ting Tao, Xu-Bing Li, Dong-Dong Chen, Hao Jin, Xiao-Yan Geng, Yi Wang, Shi-Fa Gu, Wen Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title | Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title_full | Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title_fullStr | Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title_full_unstemmed | Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title_short | Synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
title_sort | synthesis and biological evaluation of 2-aryl-benzimidazole derivatives of dehydroabietic acid as novel tubulin polymerization inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080489/ https://www.ncbi.nlm.nih.gov/pubmed/35539265 http://dx.doi.org/10.1039/c8ra02078g |
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