1. Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR.
- Author
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Khattab RR, Alshamari AK, Hassan AA, Elganzory HH, El-Sayed WA, Awad HM, Nossier ES, and Hassan NA
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Cell Survival drug effects, Click Chemistry, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Glycosides chemistry, Humans, Molecular Structure, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyrimidines chemistry, Structure-Activity Relationship, Triazoles chemistry, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Glycosides pharmacology, Molecular Docking Simulation, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology, Triazoles pharmacology
- Abstract
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.
- Published
- 2021
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