Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities...

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Main Authors:	Tarek S. Ibrahim, Mohamed M. Hawwas, Azizah M. Malebari, Ehab S. Taher, Abdelsattar M. Omar, Niamh M. O’Boyle, Eavan McLoughlin, Zakaria K. Abdel-Samii, Yaseen A. M. M. Elshaier
Format:	Article
Language:	English
Published:	MDPI AG 2020-11-01
Series:	Pharmaceuticals
Subjects:	combretastatin A-4 quinoline tubulin apoptosis hydrazone oxadiazole
Online Access:	https://www.mdpi.com/1424-8247/13/11/393

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spelling	doaj-19ebe3e124bc42398900ea3767719fa52020-11-25T04:09:17ZengMDPI AGPharmaceuticals1424-82472020-11-011339339310.3390/ph13110393Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin ActivityTarek S. Ibrahim0Mohamed M. Hawwas1Azizah M. Malebari2Ehab S. Taher3Abdelsattar M. Omar4Niamh M. O’Boyle5Eavan McLoughlin6Zakaria K. Abdel-Samii7Yaseen A. M. M. Elshaier8Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaSchool of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Dublin 2, IrelandSchool of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Dublin 2, IrelandDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, 32958 Menoufia, EgyptA novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound,<b> 19h</b>, demonstrated superior IC<sub>50</sub> values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting <b>19h</b>’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, <b>19h </b>caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that <b>19h</b> holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.https://www.mdpi.com/1424-8247/13/11/393combretastatin A-4quinolinetubulinapoptosishydrazoneoxadiazole
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Tarek S. Ibrahim Mohamed M. Hawwas Azizah M. Malebari Ehab S. Taher Abdelsattar M. Omar Niamh M. O’Boyle Eavan McLoughlin Zakaria K. Abdel-Samii Yaseen A. M. M. Elshaier
spellingShingle	Tarek S. Ibrahim Mohamed M. Hawwas Azizah M. Malebari Ehab S. Taher Abdelsattar M. Omar Niamh M. O’Boyle Eavan McLoughlin Zakaria K. Abdel-Samii Yaseen A. M. M. Elshaier Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity Pharmaceuticals combretastatin A-4 quinoline tubulin apoptosis hydrazone oxadiazole
author_facet	Tarek S. Ibrahim Mohamed M. Hawwas Azizah M. Malebari Ehab S. Taher Abdelsattar M. Omar Niamh M. O’Boyle Eavan McLoughlin Zakaria K. Abdel-Samii Yaseen A. M. M. Elshaier
author_sort	Tarek S. Ibrahim
title	Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
title_short	Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
title_full	Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
title_fullStr	Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
title_full_unstemmed	Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
title_sort	potent quinoline-containing combretastatin a-4 analogues: design, synthesis, antiproliferative, and anti-tubulin activity
publisher	MDPI AG
series	Pharmaceuticals
issn	1424-8247
publishDate	2020-11-01
description	A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound,<b> 19h</b>, demonstrated superior IC<sub>50</sub> values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting <b>19h</b>’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, <b>19h </b>caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that <b>19h</b> holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.
topic	combretastatin A-4 quinoline tubulin apoptosis hydrazone oxadiazole
url	https://www.mdpi.com/1424-8247/13/11/393
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Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

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