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Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different ca...

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Autores principales: Ibrahim, Tarek S., Hawwas, Mohamed M., Malebari, Azizah M., Taher, Ehab S., Omar, Abdelsattar M., Neamatallah, Thikryat, Abdel-Samii, Zakaria K., Safo, Martin K., Elshaier, Yaseen A. M. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993375/
https://www.ncbi.nlm.nih.gov/pubmed/33730937
http://dx.doi.org/10.1080/14756366.2021.1899168
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author Ibrahim, Tarek S.
Hawwas, Mohamed M.
Malebari, Azizah M.
Taher, Ehab S.
Omar, Abdelsattar M.
Neamatallah, Thikryat
Abdel-Samii, Zakaria K.
Safo, Martin K.
Elshaier, Yaseen A. M. M.
author_facet Ibrahim, Tarek S.
Hawwas, Mohamed M.
Malebari, Azizah M.
Taher, Ehab S.
Omar, Abdelsattar M.
Neamatallah, Thikryat
Abdel-Samii, Zakaria K.
Safo, Martin K.
Elshaier, Yaseen A. M. M.
author_sort Ibrahim, Tarek S.
collection PubMed
description A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC(50) ranging from 0.010 to 0.042 µM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G(2)/M phase arrest. Besides, 12c induces apoptosis via HIGHLIGHTS: A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [(3)H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G(2)/M phase, effectively inducing apoptosis and inhibition of cell migration.
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spelling pubmed-79933752021-03-31 Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect Ibrahim, Tarek S. Hawwas, Mohamed M. Malebari, Azizah M. Taher, Ehab S. Omar, Abdelsattar M. Neamatallah, Thikryat Abdel-Samii, Zakaria K. Safo, Martin K. Elshaier, Yaseen A. M. M. J Enzyme Inhib Med Chem Research Paper A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC(50) ranging from 0.010 to 0.042 µM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G(2)/M phase arrest. Besides, 12c induces apoptosis via HIGHLIGHTS: A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [(3)H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G(2)/M phase, effectively inducing apoptosis and inhibition of cell migration. Taylor & Francis 2021-03-18 /pmc/articles/PMC7993375/ /pubmed/33730937 http://dx.doi.org/10.1080/14756366.2021.1899168 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
Ibrahim, Tarek S.
Hawwas, Mohamed M.
Malebari, Azizah M.
Taher, Ehab S.
Omar, Abdelsattar M.
Neamatallah, Thikryat
Abdel-Samii, Zakaria K.
Safo, Martin K.
Elshaier, Yaseen A. M. M.
Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title_full Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title_fullStr Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title_full_unstemmed Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title_short Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
title_sort discovery of novel quinoline-based analogues of combretastatin a-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993375/
https://www.ncbi.nlm.nih.gov/pubmed/33730937
http://dx.doi.org/10.1080/14756366.2021.1899168
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