Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR
| Autor: | Allam A. Hassan, Hanem M. Awad, Asma K Alshamari, Nasser A. Hassan, Reham R. Khattab, Eman S. Nossier, Hussein H Elganzory, Wael A. El-Sayed |
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| Rok vydání: | 2021 |
| Předmět: |
Cell Survival
EGFR Triazole Antineoplastic Agents RM1-950 anticancer 01 natural sciences chemistry.chemical_compound Structure-Activity Relationship Gefitinib Drug Discovery medicine Tumor Cells Cultured Cytotoxic T cell Humans MTT assay Doxorubicin Protein Kinase Inhibitors Cell Proliferation Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Click chemistry Glycoside glycosides General Medicine Triazoles Combinatorial chemistry 0104 chemical sciences ErbB Receptors Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Enzyme Pyrimidines Therapeutics. Pharmacology Drug Screening Assays Antitumor thienopyrimidines medicine.drug Research Article Research Paper |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry article-version (VoR) Version of Record Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 504-516 (2021) |
| DOI: | 10.6084/m9.figshare.13655461 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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