Novel structure-activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators

Claudius Coburger, Jörg Wollmann, Martin Krug, Christiane Baumert, Marianne Seifert, Joséf Molnár, Hermann Lage, Andreas Hilgeroth

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP) 1 and MRP2 inhibition are discussed and prove to be mainly determined by certain aromatic substitution patterns. The characterization of breast cancer resistance protein (BCRP) inhibition results in the discovery of benzyloxy substituted derivatives as selective P-gp inhibitors.

Original languageEnglish
Pages (from-to)4983-4990
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number14
DOIs
Publication statusPublished - Jul 15 2010

Keywords

  • Breast cancer resistant protein (BCRP)
  • Multidrug resistance (MDR)
  • Multidrug resistance associated protein (MRP)
  • P-Glycoprotein (P-gp)
  • Selectivity
  • Structure-activity relationships (SAR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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