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Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity
A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363846/ https://www.ncbi.nlm.nih.gov/pubmed/28333984 http://dx.doi.org/10.1371/journal.pone.0174006 |
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author | Sun, Maolin Xu, Qile Xu, Jingwen Wu, Yue Wang, Yueting Zuo, Daiying Guan, Qi Bao, Kai Wang, Jian Wu, Yingliang Zhang, Weige |
author_facet | Sun, Maolin Xu, Qile Xu, Jingwen Wu, Yue Wang, Yueting Zuo, Daiying Guan, Qi Bao, Kai Wang, Jian Wu, Yingliang Zhang, Weige |
author_sort | Sun, Maolin |
collection | PubMed |
description | A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G(2)/M phase in both concentration- and time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin. |
format | Online Article Text |
id | pubmed-5363846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53638462017-04-06 Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity Sun, Maolin Xu, Qile Xu, Jingwen Wu, Yue Wang, Yueting Zuo, Daiying Guan, Qi Bao, Kai Wang, Jian Wu, Yingliang Zhang, Weige PLoS One Research Article A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G(2)/M phase in both concentration- and time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin. Public Library of Science 2017-03-23 /pmc/articles/PMC5363846/ /pubmed/28333984 http://dx.doi.org/10.1371/journal.pone.0174006 Text en © 2017 Sun et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sun, Maolin Xu, Qile Xu, Jingwen Wu, Yue Wang, Yueting Zuo, Daiying Guan, Qi Bao, Kai Wang, Jian Wu, Yingliang Zhang, Weige Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title | Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title_full | Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title_fullStr | Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title_full_unstemmed | Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title_short | Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
title_sort | synthesis and bioevaluation of n,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363846/ https://www.ncbi.nlm.nih.gov/pubmed/28333984 http://dx.doi.org/10.1371/journal.pone.0174006 |
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