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Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors
Colchicine binding site inhibitors (CBSIs) are potential microtubule targeting agents (MTAs), which can overcome multidrug resistance, improve aqueous solubility and reduce toxicity faced by most MTAs. Novel tetrahydroquinoxaline sulfonamide derivatives were designed, synthesized and evaluated for t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577396/ https://www.ncbi.nlm.nih.gov/pubmed/37849704 http://dx.doi.org/10.1039/d3ra05720h |
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author | Dong, Haiyang Lu, Lu Song, Xueting Li, Youkang Zhou, Jinguang Xu, Yungen Zhang, Yahong Qi, Jianguo Liang, Tingting Wang, Jianhong |
author_facet | Dong, Haiyang Lu, Lu Song, Xueting Li, Youkang Zhou, Jinguang Xu, Yungen Zhang, Yahong Qi, Jianguo Liang, Tingting Wang, Jianhong |
author_sort | Dong, Haiyang |
collection | PubMed |
description | Colchicine binding site inhibitors (CBSIs) are potential microtubule targeting agents (MTAs), which can overcome multidrug resistance, improve aqueous solubility and reduce toxicity faced by most MTAs. Novel tetrahydroquinoxaline sulfonamide derivatives were designed, synthesized and evaluated for their antiproliferative activities. The MTT assay results demonstrated that some derivatives exhibited moderate to strong inhibitory activities against HT-29 cell line. Among them, compound I-7 was the most active compound. Moreover, I-7 inhibited tubulin polymerization, disturbed microtubule network, disrupted the formation of mitotic spindle and arrested cell cycle at G2/M phase. However, I-7 didn't induce cell apoptosis. Furthermore, the prediction of ADME demonstrated that I-7 showed favorable physiochemical and pharmacokinetic properties. And the detailed molecular docking confirmed I-7 targeted the site of colchicine through hydrogen and hydrophobic interactions. |
format | Online Article Text |
id | pubmed-10577396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-105773962023-10-17 Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors Dong, Haiyang Lu, Lu Song, Xueting Li, Youkang Zhou, Jinguang Xu, Yungen Zhang, Yahong Qi, Jianguo Liang, Tingting Wang, Jianhong RSC Adv Chemistry Colchicine binding site inhibitors (CBSIs) are potential microtubule targeting agents (MTAs), which can overcome multidrug resistance, improve aqueous solubility and reduce toxicity faced by most MTAs. Novel tetrahydroquinoxaline sulfonamide derivatives were designed, synthesized and evaluated for their antiproliferative activities. The MTT assay results demonstrated that some derivatives exhibited moderate to strong inhibitory activities against HT-29 cell line. Among them, compound I-7 was the most active compound. Moreover, I-7 inhibited tubulin polymerization, disturbed microtubule network, disrupted the formation of mitotic spindle and arrested cell cycle at G2/M phase. However, I-7 didn't induce cell apoptosis. Furthermore, the prediction of ADME demonstrated that I-7 showed favorable physiochemical and pharmacokinetic properties. And the detailed molecular docking confirmed I-7 targeted the site of colchicine through hydrogen and hydrophobic interactions. The Royal Society of Chemistry 2023-10-16 /pmc/articles/PMC10577396/ /pubmed/37849704 http://dx.doi.org/10.1039/d3ra05720h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Dong, Haiyang Lu, Lu Song, Xueting Li, Youkang Zhou, Jinguang Xu, Yungen Zhang, Yahong Qi, Jianguo Liang, Tingting Wang, Jianhong Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title | Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title_full | Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title_fullStr | Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title_full_unstemmed | Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title_short | Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
title_sort | design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577396/ https://www.ncbi.nlm.nih.gov/pubmed/37849704 http://dx.doi.org/10.1039/d3ra05720h |
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