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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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
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.
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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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