Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR
In the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13–18 was studied against HCT-116 and MC...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2021-01-01
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Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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Online Access: | http://dx.doi.org/10.1080/14756366.2020.1871335 |
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author | Reham R. Khattab Asma K. Alshamari Allam A. Hassan Hussein H. Elganzory Wael A. El-Sayed Hanem M. Awad Eman S. Nossier Nasser A. Hassan |
author_facet | Reham R. Khattab Asma K. Alshamari Allam A. Hassan Hussein H. Elganzory Wael A. El-Sayed Hanem M. Awad Eman S. Nossier Nasser A. Hassan |
author_sort | Reham R. Khattab |
collection | DOAJ |
description | In the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13–18 was studied against HCT-116 and MCF-7 cell lines by the MTT assay. The triazole glycosides 16 and 18 provided significant cytotoxic activities against HCT-116 cell lines comparable to that of doxorubicin and other studied compounds. The cytotoxic behaviour against MCF-7 exhibited that all the investigated compounds were more potent than doxorubicin. Moreover, all screened targets were evaluated against mutant EGFR kinase type L858R and the results revealed that the acetylated 1,2,3-triazole glycosides 13–18 exhibited excellent EGFR inhibitory activity in comparison with gefitinib. Furthermore, molecular modelling studies were performed to investigate the binding affinity of the most active compounds to EGFR enzyme. |
first_indexed | 2024-04-11T15:44:33Z |
format | Article |
id | doaj.art-4220b9217cba473785711b9e789c32b7 |
institution | Directory Open Access Journal |
issn | 1475-6366 1475-6374 |
language | English |
last_indexed | 2024-04-11T15:44:33Z |
publishDate | 2021-01-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Journal of Enzyme Inhibition and Medicinal Chemistry |
spelling | doaj.art-4220b9217cba473785711b9e789c32b72022-12-22T04:15:37ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136150451610.1080/14756366.2020.18713351871335Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFRReham R. Khattab0Asma K. Alshamari1Allam A. Hassan2Hussein H. Elganzory3Wael A. El-Sayed4Hanem M. Awad5Eman S. Nossier6Nasser A. Hassan7Photochemistry Department (Synthetic Unit), National Research CentreChemistry Department, College of Science, Ha'il UniversityChemistry Department, Faculty of Science, Suez UniversityDepartment of Chemistry, College of Science, Qassim UniversityPhotochemistry Department (Synthetic Unit), National Research CentreTanning Materials and Leather Technology Department, National Research CentrePharmaceutical Medicinal Chemistry, Faculty of Pharmacy (Girls), Al-Azhar UniversityPhotochemistry Department (Synthetic Unit), National Research CentreIn the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13–18 was studied against HCT-116 and MCF-7 cell lines by the MTT assay. The triazole glycosides 16 and 18 provided significant cytotoxic activities against HCT-116 cell lines comparable to that of doxorubicin and other studied compounds. The cytotoxic behaviour against MCF-7 exhibited that all the investigated compounds were more potent than doxorubicin. Moreover, all screened targets were evaluated against mutant EGFR kinase type L858R and the results revealed that the acetylated 1,2,3-triazole glycosides 13–18 exhibited excellent EGFR inhibitory activity in comparison with gefitinib. Furthermore, molecular modelling studies were performed to investigate the binding affinity of the most active compounds to EGFR enzyme.http://dx.doi.org/10.1080/14756366.2020.1871335click chemistrythienopyrimidinesglycosidesanticanceregfr |
spellingShingle | Reham R. Khattab Asma K. Alshamari Allam A. Hassan Hussein H. Elganzory Wael A. El-Sayed Hanem M. Awad Eman S. Nossier Nasser A. Hassan Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR Journal of Enzyme Inhibition and Medicinal Chemistry click chemistry thienopyrimidines glycosides anticancer egfr |
title | Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR |
title_full | Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR |
title_fullStr | Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR |
title_full_unstemmed | Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR |
title_short | Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR |
title_sort | click chemistry based synthesis cytotoxic activity and molecular docking of novel triazole thienopyrimidine hybrid glycosides targeting egfr |
topic | click chemistry thienopyrimidines glycosides anticancer egfr |
url | http://dx.doi.org/10.1080/14756366.2020.1871335 |
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