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Identification of selenocompounds with promising properties to reverse cancer multidrug resistance
Enrique Domínguez-Álvarez1, Márió Gajdács2, Gabriella Spengler2
1Department 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.
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.
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