Identification of selenocompounds with promising properties to reverse cancer multidrug resistance

Bioorg Med Chem Lett. 2016 Jun 15;26(12):2821-2824. doi: 10.1016/j.bmcl.2016.04.064. Epub 2016 Apr 22.

Abstract

In previous studies, 56 novel selenoesters and one cyclic selenoanhydride with chemopreventive, antiproliferative and cytotoxic activity were described. Herein, the selenoanhydride and selected selenoesters were evaluated for their ability to reverse the cancer multidrug resistance (MDR) using the ABCB1 efflux pump inhibition assay in mouse MDR T-lymphoma cells. Results showed that the selenoanhydride (1) and the selenoesters with ketone terminal fragments (9-11) exerted (1.7-3.6)-fold stronger efflux pump inhibitory action than the reference verapamil. In addition, those four derivatives triggered apoptotic events in more than 80% of the examined MDR mouse cells.

Keywords: ABCB1 efflux pump (P-glycoprotein); Apoptosis; Cancer; MDR efflux pumps; Multidrug resistance (MDR); Selenium; Selenoesters.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / pathology
  • Mice
  • Molecular Structure
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Organoselenium Compounds