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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MDPI AG
2021-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/22/6798 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:14:49Z |
| format | Article |
| id | doaj.art-7610b55466f44c70935154c1ed148189 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:14:49Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7610b55466f44c70935154c1ed1481892023-11-23T00:33:54ZengMDPI AGMolecules1420-30492021-11-012622679810.3390/molecules26226798Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative AgentsEssmat M. El-Sheref0Mohammed A. I. Elbastawesy1Alan B. Brown2Ahmed M. Shawky3Hesham A. M. Gomaa4Stefan Bräse5Bahaa G. M. Youssif6Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptProgram in Chemistry, Florida Institute of Technology, 150 W University Blvd, Melbourne, FL 32901, USAScience and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi ArabiaPharmacology Department, College of Pharmacy, Jouf University, Sakaka 72314, Saudi ArabiaInstitute of Organic Chemistry, Karlsruhe Institute of Technology, 76131 Karlsruhe, GermanyPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptA 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.https://www.mdpi.com/1420-3049/26/22/6798clickazidoquinolonestriazoleanti-proliferativeapoptosis |
| spellingShingle | 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 Molecules click azido quinolones triazole anti-proliferative apoptosis |
| 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_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_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_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 |
| topic | click azido quinolones triazole anti-proliferative apoptosis |
| url | https://www.mdpi.com/1420-3049/26/22/6798 |
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