2. Academic Validation
  3. Identification of selenocompounds with promising properties to reverse cancer multidrug resistance

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.
Enrique Domínguez-Álvarez 1,  Márió Gajdács 2,  Gabriella Spengler 2,  Juan Antonio Palop 3,  Małgorzata Anna Marć 4,  Katarzyna Kieć-Kononowicz 4,  Leonard Amaral 2,  Joseph Molnár 2,  Claus Jacob 5,  Jadwiga Handzlik 4,  Carmen Sanmartín 3
Affiliations

Affiliations

  • 1 Department of Organic and Pharmaceutical Chemistry, School of Pharmacy, University of Navarra, Irunlarrea 1, 31010 Pamplona, Spain; Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
  • 2 Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.
  • 3 Department of Organic and Pharmaceutical Chemistry, School of Pharmacy, University of Navarra, Irunlarrea 1, 31010 Pamplona, Spain.
  • 4 Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
  • 5 Division of Bioorganic Chemistry, Saarland State University, Campus, Geb. B2.1, 66123, Saarbruecken, Germany.
PMID: 27156771 DOI: 10.1016/j.bmcl.2016.04.064
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.

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