Quercetin-POM (pivaloxymethyl) conjugates: Modulatory activity for P-glycoprotein-based multidrug resistance

Mi Kyoung Kim, Kwang Su Park, Hyunah Choo, Youhoon Chong

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background We previously demonstrated that the bioactivity of quercetin could be improved through conjugation with a hydrolysable pivaloxymethyl (POM) group. Purpose Present study aimed to evaluate MDR (multidrug resistance)-modulatory activity of the quercetin-POM conjugates. Study design/methods MDR-modulatory activity was determined by measuring cytotoxicity of various anticancer agents to MDR MES-SA/Dx5 cell lines upon combination with the quercetin-POM conjugates. Results The quercetin-7-O-POM conjugate (7-O-POM-Q) was significantly more potent than quercetin in reversing MDR, which recovered the cytotoxicity of various anticancer agents with EC50 values of 1.1-1.3 μM. A series of mechanistic studies revealed that 7-O-POM-Q competes with verapamil in binding to the same drug-binding site of the major MDR target, Pgp (P-glycoprotein), and inhibits Pgp-mediated drug efflux with a similar potency as verapamil. The physicochemical properties of 7-O-POM-Q were then evaluated, which confirmed that 7-O-POM-Q has remarkably enhanced cellular uptake and intracellular localization compared with quercetin. Additionally, it is noteworthy that 7-O-POM-Q undergoes slow hydrolysis to quercetin over a prolonged period of time. Conclusion The quercetin-POM conjugate showed significantly improved MDR-reversing activity compared with quercetin, which could be attributed to its capacity to maintain high intracellular concentrations.

Original languageEnglish
Pages (from-to)778-785
Number of pages8
Issue number7-8
StatePublished - 22 Jun 2015
Externally publishedYes


  • Modulator
  • Multidrug resistance (MDR)
  • P-glycoprotein (Pgp)
  • Pivaloxymethyl
  • Quercetin


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