Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)<i>bis</i>(4-hydroxyquinolin-2(1<i>H</i>)-ones) with 4-azido-2-quinolones in good yields. This method...

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Autores principales: Essmat M. El-Sheref, Mohammed A. I. Elbastawesy, Alan B. Brown, Ahmed M. Shawky, Hesham A. M. Gomaa, Stefan Bräse, Bahaa G. M. Youssif
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/7610b55466f44c70935154c1ed148189
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spelling oai:doaj.org-article:7610b55466f44c70935154c1ed1481892021-11-25T18:27:19ZDesign and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents10.3390/molecules262267981420-3049https://doaj.org/article/7610b55466f44c70935154c1ed1481892021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6798https://doaj.org/toc/1420-3049A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)<i>bis</i>(4-hydroxyquinolin-2(1<i>H</i>)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound <b>8g</b> was the most active one, achieving IC<sub>50</sub> = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with <b>8g</b> showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.Essmat M. El-SherefMohammed A. I. ElbastawesyAlan B. BrownAhmed M. ShawkyHesham A. M. GomaaStefan BräseBahaa G. M. YoussifMDPI AGarticleclickazidoquinolonestriazoleanti-proliferativeapoptosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6798, p 6798 (2021)
institution DOAJ
collection DOAJ
language EN
topic click
azido
quinolones
triazole
anti-proliferative
apoptosis
Organic chemistry
QD241-441
spellingShingle click
azido
quinolones
triazole
anti-proliferative
apoptosis
Organic chemistry
QD241-441
Essmat M. El-Sheref
Mohammed A. I. Elbastawesy
Alan B. Brown
Ahmed M. Shawky
Hesham A. M. Gomaa
Stefan Bräse
Bahaa G. M. Youssif
Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
description A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)<i>bis</i>(4-hydroxyquinolin-2(1<i>H</i>)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound <b>8g</b> was the most active one, achieving IC<sub>50</sub> = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with <b>8g</b> showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.
format article
author Essmat M. El-Sheref
Mohammed A. I. Elbastawesy
Alan B. Brown
Ahmed M. Shawky
Hesham A. M. Gomaa
Stefan Bräse
Bahaa G. M. Youssif
author_facet Essmat M. El-Sheref
Mohammed A. I. Elbastawesy
Alan B. Brown
Ahmed M. Shawky
Hesham A. M. Gomaa
Stefan Bräse
Bahaa G. M. Youssif
author_sort Essmat M. El-Sheref
title Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
title_short Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
title_full Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
title_fullStr Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
title_full_unstemmed Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
title_sort design and synthesis of (2-<i>oxo</i>-1,2-dihydroquinolin-4-yl)-1,2,3-triazole derivatives via click reaction: potential apoptotic antiproliferative agents
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/7610b55466f44c70935154c1ed148189
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