Xanthone analogues as potent modulators of intestinal P-glycoprotein

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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Intestinal P-glycoprotein (P-gp) is a limiting step for oral absorption of drugs. Therefore, P-gp inhibitors have been studied as enhancers of oral absorption of drugs that are P-gp substrates. We investigated the in vitro and in vivo P-gp inhibitory activity of synthesized xanthone analogues. With 3-(3-chloro-2-hydroxypropoxy)-1-hydroxy-9H-thioxanthen-9-one, compound 13, accumulation of daunomycin (DNM) increased 707% and efflux of DNM decreased 66% compared to DNM alone. Relative bioavailability (RB) of paclitaxel (PTX, 25 mg/kg) increased 2.5-fold after oral administration with 13 (5 mg/kg). In a xenograft animal model, oral administration of PTX (40 mg/kg) with 13 (10 mg/kg) significantly inhibited tumour growth and was more effective than intravenously administered PTX (10 mg/kg) alone. Therefore, the synthesized xanthone analogue 13 might have therapeutic benefits for oral absorption of P-gp substrate anticancer drugs.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 26 Mar 2015

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (Basic Science Research Program: 2011-0005990 ).

Publisher Copyright:
© 2015 Published by Elsevier Masson SAS.


  • Bioavailability
  • P-glycoprotein inhibitor
  • Paclitaxel
  • Xanthone analogue
  • Xenograft


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