Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer

A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells wit...

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Autores principales: Ding, Lijuan, Wei, Feng, Wang, Nanya, Sun, Yue, Wang, Qiang, Fan, Xia, Qi, Ling, Wang, Shudong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291071/
https://www.ncbi.nlm.nih.gov/pubmed/34281464
http://dx.doi.org/10.1080/14756366.2021.1917564
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author Ding, Lijuan
Wei, Feng
Wang, Nanya
Sun, Yue
Wang, Qiang
Fan, Xia
Qi, Ling
Wang, Shudong
author_facet Ding, Lijuan
Wei, Feng
Wang, Nanya
Sun, Yue
Wang, Qiang
Fan, Xia
Qi, Ling
Wang, Shudong
author_sort Ding, Lijuan
collection PubMed
description A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells with an IC(50) value of 0.32 μM. Compound 17a could effectively inhibit tubulin polymerisation with an IC(50) value of 1.27 μM. Meanwhile, it selectively suppressed LSD1 with an IC(50) value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide 17a exhibited the potent antitumor activity in vivo. All these findings revealed that compound 17a might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer.
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spelling pubmed-82910712021-08-03 Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer Ding, Lijuan Wei, Feng Wang, Nanya Sun, Yue Wang, Qiang Fan, Xia Qi, Ling Wang, Shudong J Enzyme Inhib Med Chem Research Paper A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells with an IC(50) value of 0.32 μM. Compound 17a could effectively inhibit tubulin polymerisation with an IC(50) value of 1.27 μM. Meanwhile, it selectively suppressed LSD1 with an IC(50) value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide 17a exhibited the potent antitumor activity in vivo. All these findings revealed that compound 17a might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer. Taylor & Francis 2021-07-19 /pmc/articles/PMC8291071/ /pubmed/34281464 http://dx.doi.org/10.1080/14756366.2021.1917564 Text en © 2021 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
Ding, Lijuan
Wei, Feng
Wang, Nanya
Sun, Yue
Wang, Qiang
Fan, Xia
Qi, Ling
Wang, Shudong
Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title_full Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title_fullStr Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title_full_unstemmed Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title_short Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer
title_sort tertiary sulphonamide derivatives as dual acting small molecules that inhibit lsd1 and suppress tubulin polymerisation against liver cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291071/
https://www.ncbi.nlm.nih.gov/pubmed/34281464
http://dx.doi.org/10.1080/14756366.2021.1917564
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