Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers
Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Future medicinal chemistry - 15(2023), 19 vom: 26. Okt., Seite 1773-1790 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gaber, Ahmed A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0156 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363741909 |
|---|
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| 245 | 1 | 0 | |a Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers |
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| 500 | |a Date Revised 13.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a EGFR TKIs | |
| 650 | 4 | |a EGFR-T790M | |
| 650 | 4 | |a EGFR-WT | |
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| 650 | 4 | |a pyrazolopyrimidine | |
| 650 | 7 | |a ErbB Receptors |2 NLM | |
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| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a EGFR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Sharaky, Marwa |e verfasserin |4 aut | |
| 700 | 1 | |a Elmaaty, Ayman Abo |e verfasserin |4 aut | |
| 700 | 1 | |a Hammouda, Mohamed M |e verfasserin |4 aut | |
| 700 | 1 | |a Mourad, Ahmed Ae |e verfasserin |4 aut | |
| 700 | 1 | |a Elkhawaga, Samy Y |e verfasserin |4 aut | |
| 700 | 1 | |a Mokhtar, Mahmoud Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Abouzied, Amr S |e verfasserin |4 aut | |
| 700 | 1 | |a Mourad, Mai Ae |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Karmalawy, Ahmed A |e verfasserin |4 aut | |
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