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...
Guardado en:
Autores principales: | , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
MDPI AG
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/7610b55466f44c70935154c1ed148189 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:7610b55466f44c70935154c1ed148189 |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT essmatmelsheref designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT mohammedaielbastawesy designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT alanbbrown designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT ahmedmshawky designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT heshamamgomaa designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT stefanbrase designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents AT bahaagmyoussif designandsynthesisof2ioxoi12dihydroquinolin4yl123triazolederivativesviaclickreactionpotentialapoptoticantiproliferativeagents |
_version_ |
1718411139110404096 |