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

Tam Q. Dinh, Charles Smith, Xiaohui Du, Robert W. Armstrong

Research output: Contribution to journalArticle

46 Scopus citations

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 languageEnglish (US)
Pages (from-to)981-987
Number of pages7
JournalJournal of Medicinal Chemistry
Volume41
Issue number6
DOIs
StatePublished - Mar 12 1998

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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