Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells

Jian Yuan, Iris L K Wong, Tao Jiang, Si Wen Wang, Tao Liu, Bin Jin Wen, Ming Cheung Chow, Biao Wan Sheng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

50 Citations (Scopus)


Three methylated quercetins and a series of O-3 substituted 5,7,3′,4′-tetra-O-methylated quercetin derivatives have been synthesized and evaluated on the modulating activity of P-gp, BCRP and MRP1 in cancer cell lines. Compound 17 (with a 2-((4-methoxybenzoyl)oxy)ethyl at O-3) is the most potent P-gp modulator. Three derivatives, compound 9 (3,7,3′,4′-tetra-O-methylated quercetin), compound 14 (with a 2-((3-oxo-3-(3,4,5trimethoxyphenyl)prop-1-en-1-yl)oxy)ethyl at O-3) and compound 17, consistently exhibited promising BCRP-modulating activity. Interestingly, compound 17 was found to be equipotent against both P-gp and BCRP. Importantly, these synthetic quercetin derivatives did not exhibit any inherent cytotoxicity to cancer cell lines or normal mouse fibroblast cell lines. These quercetin derivatives can be employed as safe and effective modulators of P-gp- or BCRP-mediated drug resistance in cancer.
Original languageEnglish
Pages (from-to)413-422
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 1 Aug 2012


  • BCRP
  • Methylated quercetin derivatives
  • MRP1
  • Multidrug resistance (MDR)
  • P-gp
  • Quercetin

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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