Design, Synthesis, and Evaluation of the Multidrug Resistance-Reversing Activity of d -Glucose Mimetics of Hapalosin
| Autor: | Tam Q. Dinh, Xiaohui Du, Robert W. Armstrong, Charles D. Smith |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Lactams
Cell Survival Stereochemistry ATP-binding cassette transporter Chemical synthesis Lactones Depsipeptides Drug Discovery Tumor Cells Cultured Humans ATP Binding Cassette Transporter Subfamily B Member 1 Cytotoxicity P-glycoprotein Depsipeptide biology Chemistry Molecular Mimicry Drug Resistance Multiple In vitro Multiple drug resistance Glucose Biochemistry Drug Resistance Neoplasm Drug Design biology.protein Molecular Medicine ATP-Binding Cassette Transporters Multidrug Resistance-Associated Proteins |
| Zdroj: | Journal of Medicinal Chemistry. 41:981-987 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | When five substituents of hapalosin were placed on D-glucose, molecular modeling revealed that the substituents on mimetics 2 and 3 occupy similar spatial positions as the corresponding substituents on hapalosin. Mimetic 3 and all the glucopyranoside intermediates generated in its synthesis were assessed for their ability to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) or the multidrug resistance-associated protein (MRP). None of the sugar compounds were as effective as hapalosin in inhibiting P-gp in cytotoxicity and drug accumulation assays using MCF-7/ADR cells. By contrast, four D-glucose compounds exhibited similar efficacy as hapalosin in antagonizing MRP in cytotoxicity assays with HL-60/ADR cells. |
| Databáze: | OpenAIRE |
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