Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Biological Evaluation of Phenoxy-N-phenylacetamide Derivatives as Novel P-glycoprotein Inhibitors

  • Lee, Kyeong (College of Pharmacy, Dongguk University-Seoul) ;
  • Roh, Sang-Hee (Korea BK21 Project Team, College of Pharmacy, Chosun University) ;
  • Xia, Yan (College of Pharmacy, Dongguk University-Seoul) ;
  • Kang, Keon-Wook (College of Pharmacy, Seoul National University)
  • Received : 2011.07.18
  • Accepted : 2011.08.16
  • Published : 2011.10.20
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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.

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