Flavonoid-Related Modulators of Multidrug Resistance: Synthesis, Pharmacological Activity, and Structure−Activity Relationships
| Autor: | Yves Rolland, Marc A. Schwaller, Genevieve Chapuis, Guy Lewin, Jean-Marc Kühnel, Jacques Ferte |
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| Rok vydání: | 1999 |
| Předmět: |
Magnetic Resonance Spectroscopy
Chemical synthesis Mass Spectrometry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans Cytotoxicity P-glycoprotein Flavonoids Antibiotics Antineoplastic biology Biological activity Calcium Channel Blockers Drug Resistance Multiple In vitro Multiple drug resistance Verapamil chemistry Biochemistry Doxorubicin Lipophilicity biology.protein Molecular Medicine K562 Cells Flavanone |
| Zdroj: | Journal of Medicinal Chemistry. 42:478-489 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm981064b |
| Popis: | A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 microM, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR-modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3, 4-trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent than verapamil. |
| Databáze: | OpenAIRE |
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