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Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells
Aim:A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors. Materials and methods: Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids again...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973347/ https://www.ncbi.nlm.nih.gov/pubmed/35350943 http://dx.doi.org/10.1080/14756366.2021.2014830 |
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author | Liu, Jia Zhu, Xingwang Yu, Liu Mao, Minghuan |
author_facet | Liu, Jia Zhu, Xingwang Yu, Liu Mao, Minghuan |
author_sort | Liu, Jia |
collection | PubMed |
description | Aim:A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors. Materials and methods: Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids against LSD1 were performed. Conclusion: sulphonamide derivative L8 exhibited the antiproliferative activity against HTB5, HTB3, HT1376, and HTB1 cells with IC(50) values of 1.87, 0.18, 0.09, and 0.93 μM, respectively. Compound L8 as a selective and reversible LSD1 inhibitor could inhibit LSD1 with the IC(50) value of 60 nM. It effectively inhibited LSD1 by increasing the expression levels of H3K4me1, H3K4me2, and H3K9me2 in HT1376 cells. To the best of our knowledge, this was the first report which showed that sulphonamide–quinoline–dithiocarbamate hybrids potently inhibited LSD1 in bladder cancer cells. Our studies give the potential application of the sulphonamide-based scaffold for developing LSD1 inhibitors to treat bladder cancer. |
format | Online Article Text |
id | pubmed-8973347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-89733472022-04-02 Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells Liu, Jia Zhu, Xingwang Yu, Liu Mao, Minghuan J Enzyme Inhib Med Chem Research Paper Aim:A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors. Materials and methods: Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids against LSD1 were performed. Conclusion: sulphonamide derivative L8 exhibited the antiproliferative activity against HTB5, HTB3, HT1376, and HTB1 cells with IC(50) values of 1.87, 0.18, 0.09, and 0.93 μM, respectively. Compound L8 as a selective and reversible LSD1 inhibitor could inhibit LSD1 with the IC(50) value of 60 nM. It effectively inhibited LSD1 by increasing the expression levels of H3K4me1, H3K4me2, and H3K9me2 in HT1376 cells. To the best of our knowledge, this was the first report which showed that sulphonamide–quinoline–dithiocarbamate hybrids potently inhibited LSD1 in bladder cancer cells. Our studies give the potential application of the sulphonamide-based scaffold for developing LSD1 inhibitors to treat bladder cancer. Taylor & Francis 2022-03-30 /pmc/articles/PMC8973347/ /pubmed/35350943 http://dx.doi.org/10.1080/14756366.2021.2014830 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://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/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Liu, Jia Zhu, Xingwang Yu, Liu Mao, Minghuan Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title | Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title_full | Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title_fullStr | Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title_full_unstemmed | Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title_short | Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells |
title_sort | discovery of novel sulphonamide hybrids that inhibit lsd1 against bladder cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973347/ https://www.ncbi.nlm.nih.gov/pubmed/35350943 http://dx.doi.org/10.1080/14756366.2021.2014830 |
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