Phthalazone tethered 1,2,3-triazole conjugates : In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities
Copyright © 2023 Elsevier Inc. All rights reserved..
New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; 1H, 13C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38. The antiproliferative assessment of derivatives 12-21 showed potent activity of compounds 16, 18, and 21 compared to the anticancer drug doxorubicin. Compound 16 showed selectivity (SI) towardthe tested cell lines ranging from 3.35 to 8.84 when compared to Dox., that showed SI ranged from 0.75 to 1.61. Derivatives 16, 18 and 21 were assessed towards VEGFR-2 inhibitory activity and result in that derivative 16 showed the potent activity (IC50 = 0.123 µM) in comparison with sorafenib (IC50 = 0.116 µM). Compound 16 caused an interference with the cell cycle distribution of MCF7 and increased the percentage of cells in S phase by 1.37-fold. In silico molecular docking of the effective derivatives 16, 18, and 21 against vascular endothelial growth factor receptor-2 (VEGFR-2) confirmed the formation of stable protein-ligand interactions within the pocket.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:133 |
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| Enthalten in: |
Bioorganic chemistry - 133(2023) vom: 09. Apr., Seite 106404 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdelgawad, Mohamed A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.01.2024 Date Revised 24.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2023.106404 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Abdelgawad, Mohamed A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phthalazone tethered 1,2,3-triazole conjugates |b In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities |
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| 500 | |a Date Revised 24.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; 1H, 13C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38. The antiproliferative assessment of derivatives 12-21 showed potent activity of compounds 16, 18, and 21 compared to the anticancer drug doxorubicin. Compound 16 showed selectivity (SI) towardthe tested cell lines ranging from 3.35 to 8.84 when compared to Dox., that showed SI ranged from 0.75 to 1.61. Derivatives 16, 18 and 21 were assessed towards VEGFR-2 inhibitory activity and result in that derivative 16 showed the potent activity (IC50 = 0.123 µM) in comparison with sorafenib (IC50 = 0.116 µM). Compound 16 caused an interference with the cell cycle distribution of MCF7 and increased the percentage of cells in S phase by 1.37-fold. In silico molecular docking of the effective derivatives 16, 18, and 21 against vascular endothelial growth factor receptor-2 (VEGFR-2) confirmed the formation of stable protein-ligand interactions within the pocket | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 1,2,3-Triazole | |
| 650 | 4 | |a Antiproliferative | |
| 650 | 4 | |a Click reaction | |
| 650 | 4 | |a Molecular docking | |
| 650 | 4 | |a Phthalazone | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a phthalylsulfathiazole |2 NLM | |
| 650 | 7 | |a 6875L5852V |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Triazoles |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor Receptor-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a phthalazone |2 NLM | |
| 700 | 1 | |a Bukhari, Syed Nasir Abbas |e verfasserin |4 aut | |
| 700 | 1 | |a Musa, Arafa |e verfasserin |4 aut | |
| 700 | 1 | |a Elmowafy, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Nayl, AbdElAziz A |e verfasserin |4 aut | |
| 700 | 1 | |a El-Ghorab, Ahmed H |e verfasserin |4 aut | |
| 700 | 1 | |a Sadek Abdel-Bakky, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Omar, Hany A |e verfasserin |4 aut | |
| 700 | 1 | |a Hadal Alotaibi, Nasser |e verfasserin |4 aut | |
| 700 | 1 | |a Hassan, Hossam M |e verfasserin |4 aut | |
| 700 | 1 | |a Ghoneim, Mohammed M |e verfasserin |4 aut | |
| 700 | 1 | |a Bakr, Rania B |e verfasserin |4 aut | |
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