Design, synthesis, and evaluation of the multidrug resistance-reversing activity of D-glucose mimetics of hapalosin

Journal of Medicinal Chemistry
Tam Q. DinhR W Armstrong

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.

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jan 1, 1989·Annual Review of Biochemistry·J A Endicott, V Ling
Mar 2, 1988·Journal of the National Cancer Institute·J A Moscow, K H Cowan

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Citations

Jun 13, 2002·Il Farmaco·E TeodoriF Gualtieri
Jun 18, 2002·Bioorganic & Medicinal Chemistry Letters·Paul V MurphyAmos B Smith
Jul 1, 1999·Bioorganic & Medicinal Chemistry Letters·C E O'ConnellC E Schwartz
Feb 15, 2000·Bioorganic & Medicinal Chemistry Letters·N KashiharaS Nishiyama
Feb 14, 2002·Chemical Reviews·Sibylle A W GrunerHorst Kessler
Jul 12, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Solida LongMadalena M M Pinto
Sep 20, 2006·ChemMedChem·Wim MeutermansBernd Becker
Jun 30, 2000·Biochemical Pharmacology·F Van BambekeP M Tulkens

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