Synthesis and biological evaluation of phenoxy-N-phenylacetamide derivatives as novel P-glycoprotein inhibitors

Kyeong Lee, Sang Hee Roh, Yan Xia, Keon Wook Kang

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Overexpression of P-glycoprotein (Pgp) is associated with multidrug resistance (MDR) of tumor cells to a number of chemotherapeutic drugs. Pgp inhibitors have been shown to effectively reverse Pgp-mediated MDR. We prepared a series of phenoxy-N-phenylacetamide derivatives and tested for their ability to inhibit Pgp as potential MDR reversing agents, using a Pgp over-expressing MCF-7/ADR cell line. Some of the synthesized compounds exhibited moderate to potent reversal activity. Of note, compound 4o showed a 3.0-fold increased inhibition compared with verapamil, a well-known Pgp inhibitor. In addition, co-treatment of the representative compound 4o and a substrate anticancer agent doxorubicin resulted in a remarkable increase in doxorubicin's antitumor effect and inhibition of DNA synthesis in the MCF-7/ADR cell line. Taken together, these findings suggest that compound 4o could be a useful lead for development of a novel Pgp inhibitor for treatment of MDR.

Original languageEnglish
Pages (from-to)3666-3674
Number of pages9
JournalBulletin of the Korean Chemical Society
Volume32
Issue number10
DOIs
StatePublished - 20 Oct 2011

Keywords

  • Chemotherapy
  • MDR reversal activity
  • Pgp
  • Phenoxy-N-phenylacetamide derivatives

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