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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...

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Autores principales: Sun, Maolin, Xu, Qile, Xu, Jingwen, Wu, Yue, Wang, Yueting, Zuo, Daiying, Guan, Qi, Bao, Kai, Wang, Jian, Wu, Yingliang, Zhang, Weige
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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.
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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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