2-Nucleobase-substituted 4,6-Diaminotriazine Analogs : Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance.
METHODS: In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, and adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types while they promoted homotypic cell-cell interaction.
RESULTS: These changes were reflected by the downregulation of matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited potent anti-angiogenic activity in vivo.
CONCLUSION: These novel nucleobase analogs reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant CRC cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Current medicinal chemistry - 30(2023), 26 vom: 11., Seite 3032-3049 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hamze, Khalil [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.06.2023 Date Revised 01.06.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/0929867329666220914112042 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346285100 |
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| 245 | 1 | 0 | |a 2-Nucleobase-substituted 4,6-Diaminotriazine Analogs |b Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells |
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| 500 | |a Date Revised 01.06.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance | ||
| 520 | |a METHODS: In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, and adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types while they promoted homotypic cell-cell interaction | ||
| 520 | |a RESULTS: These changes were reflected by the downregulation of matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited potent anti-angiogenic activity in vivo | ||
| 520 | |a CONCLUSION: These novel nucleobase analogs reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant CRC cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a 5-fluorouracil | |
| 650 | 4 | |a 6-diamino-s-triazine analogues | |
| 650 | 4 | |a Colorectal cancer | |
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| 700 | 1 | |a Abdallah, Rola H |e verfasserin |4 aut | |
| 700 | 1 | |a Younis, Nour K |e verfasserin |4 aut | |
| 700 | 1 | |a Fardoun, Manal |e verfasserin |4 aut | |
| 700 | 1 | |a Darwiche, Nadine |e verfasserin |4 aut | |
| 700 | 1 | |a Kobeissy, Firas |e verfasserin |4 aut | |
| 700 | 1 | |a Iratni, Rabah |e verfasserin |4 aut | |
| 700 | 1 | |a Bouhadir, Kamal |e verfasserin |4 aut | |
| 700 | 1 | |a Eid, Ali H |e verfasserin |4 aut | |
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