Abstract
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.
Original language | English (US) |
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Pages (from-to) | 981-987 |
Number of pages | 7 |
Journal | Journal of Medicinal Chemistry |
Volume | 41 |
Issue number | 6 |
DOIs | |
State | Published - Mar 12 1998 |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery