Identification of selenocompounds with promising properties to reverse cancer multidrug resistance. Issue 12 (15th June 2016)

• Record Type: Journal Article
• Authors: Domínguez-Álvarez, Enrique; Gajdács, Márió; Spengler, Gabriella; Palop, Juan Antonio; Marć, Małgorzata Anna; Kieć-Kononowicz, Katarzyna; Amaral, Leonard; Molnár, Joseph; Jacob, Claus; Handzlik, Jadwiga; Sanmartín, Carmen
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 12(2016)
• Page Start: 2821
• Page End: 2824
• Publication Date: 2016-06-15
• Subjects: PHPMYXRXYSBCIU-UHFFFAOYSA-N -- AWLOFFRFIIJHKA-UHFFFAOYSA-N -- UNFRMGHXKQDGNL-UHFFFAOYSA-N -- NVPAUJKABHDGEI-UHFFFAOYSA-N; Selenium -- Multidrug resistance (MDR) -- Selenoesters -- Cancer -- Apoptosis -- MDR efflux pumps -- ABCB1 efflux pump (P-glycoprotein); Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.04.064
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Further biological evaluations of active anticancer selenocompounds were performed. Their cytotoxicity, apoptosis induction and MDR reversal activity were determined. 4 compounds were (1.7–3.6)-fold stronger inhibitors of MDR pumps than verapamil. With IC50 values below 5 μM, 4 compounds were more cytotoxic than thioridazine. 4 compounds triggered apoptotic events in >80% of the examined MDR mouse cells. 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.