Synthesis, antitumour and antioxidant activities of novel α,β-unsaturated ketones and related heterocyclic analogues: EGFR inhibition and molecular modelling study
| Autor: | Magda A.-A. El-Sayed, Esam R. Ahmed, Walaa M. El-Husseiny, Alaa A.-M. Abdel-Aziz, Adel S. El-Azab, Naglaa I. Abdel-Aziz |
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| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Antioxidant Stereochemistry medicine.medical_treatment Antineoplastic Agents Pyrazoline antioxidant effect 01 natural sciences Antioxidants HeLa α β-Unsaturated ketone Structure-Activity Relationship chemistry.chemical_compound Heterocyclic Compounds Cell Line Tumor Drug Discovery medicine Humans Structure–activity relationship EGFR inhibition Protein Kinase Inhibitors IC50 Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Cell growth lcsh:RM1-950 General Medicine molecular docking Ketones biology.organism_classification In vitro 0104 chemical sciences ErbB Receptors 010404 medicinal & biomolecular chemistry lcsh:Therapeutics. Pharmacology chemistry Pyran Drug Screening Assays Antitumor antitumour activity Research Paper |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 33, Iss 1, Pp 507-518 (2018) Journal of Enzyme Inhibition and Medicinal Chemistry |
| DOI: | 10.6084/m9.figshare.5900878 |
| Popis: | New α,β-unsaturated ketones 4a,b; 5a–c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10–11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC50] ≅5.5–18.1 µΜ), in addition to significantly high ABTS•+ scavenging activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR inhibition activity with IC50 values of 0.56 and 1.6 µM, respectively, while compounds 6a and 8b showed good inhibition activity with IC50 values of 4.66 and 2.16 µM, respectively, compared with sorafenib reference drug (IC50 = 1.28 µM). Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit the binding mode towards EGFR kinase, which showed similar interaction with erlotinib. |
| Databáze: | OpenAIRE |
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