New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation
| Autor: | Patrícia M. A. Silva, Hassan Bousbaa, Madalena Pinto, Honorina Cidade, Nair Nazareth, Andreia Palmeira, Madalena Monteiro, Joana Moreira, Lucília Saraiva, Diana Ribeiro |
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| Rok vydání: | 2018 |
| Předmět: |
Quantitative Structure-Activity Relationship
Pharmaceutical Science caspase activators Alkylation 01 natural sciences Analytical Chemistry Drug Discovery heterocyclic compounds Caspase 7 chemistry.chemical_classification Molecular Structure Cell Cycle O-heterocycles apoptosis food and beverages Caspase Inhibitors 3. Good health Gene Expression Regulation Neoplastic Molecular Docking Simulation Chemistry (miscellaneous) MCF-7 Cells Alkoxy group Molecular Medicine Quantitative structure–activity relationship Cell Survival Stereochemistry Allosteric regulation Antineoplastic Agents Article lcsh:QD241-441 lcsh:Organic chemistry Prenylation Cell Line Tumor Humans antitumor activity Physical and Theoretical Chemistry alkylation Alkyl Cell Proliferation Dose-Response Relationship Drug 010405 organic chemistry Cell growth fungi Organic Chemistry Flavones 0104 chemical sciences carbohydrates (lipids) 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) flavonoids Drug Screening Assays Antitumor |
| Zdroj: | Molecules Molecules, Vol 24, Iss 1, p 129 (2018) Volume 24 Issue 1 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules24010129 |
| Popis: | The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4&ndash 28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI50 < 10 &mu M), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7. |
| Databáze: | OpenAIRE |
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