Intestinal P-glycoprotein inhibitors, benzoxanthone analogues

Song Wha Chae, Jaeok Lee, Jung Hyun Park, Youngjoo Kwon, Younghwa Na, Hwa Jeong Lee

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Objectives: The inhibitors of P-glycoprotein (P-gp) which limits an access of exogenous compounds in the luminal membrane of the intestine have been studied to enhance the intestinal P-gp-mediated absorption of anticancer drugs. Methods: Inhibition of the efflux pump by synthesized benzoxanthone derivatives was investigated in vitro and in vivo. MCF-7/ADR cell line was used for cytotoxicity assay and [3H]-daunomycin (DNM) accumulation/efflux study. Eight benzoxanthone analogues were tested for their effects on DNM cytotoxicity. Among them, three analogues were selected for the accumulation/efflux and P-gp ATPase studies. Paclitaxel (PTX), a P-gp substrate anticancer drug, was orally administered to rats with/without compound 1 (8,10-bis(thiiran-2-ylmethoxy)-7H-benzo[c]xanthen-7-one). The pharmacokinetic parameters of PTX in the presence/absence of compound 1 were evaluated from the plasma concentration-time profiles. Key-findings: Compound 1 increased the DNA accumulation to 6.5-fold and decreased the DNM efflux to approximately 1/2 in the overexpressing P-gp cell line. Relative bioavailability (RB) of PTX in rats was significantly increased up to 3.2-fold by compound 1 (0.5 or 2 mg/kg). Conclusions: Benzoxanthone analogue, compound 1 is strongly suggested to be a promising inhibitor of P-gp to improve an oral absorption of compounds for cancer therapy.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Issue number2
StatePublished - Feb 2018

Bibliographical note

Publisher Copyright:
© 2017 Royal Pharmaceutical Society


  • P-glycoprotein inhibitor
  • benzoxanthone analogue
  • intestinal P-glycoprotein
  • oral administration
  • pharmacokinetics


Dive into the research topics of 'Intestinal P-glycoprotein inhibitors, benzoxanthone analogues'. Together they form a unique fingerprint.

Cite this