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Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line

Authors :
Małgorzata Anna Marć
Carmen Sanmartín
Enrique Domínguez-Álvarez
Gabriella Spengler
Márió Gajdács
Jadwiga Handzlik
Source :
Bioorganicmedicinal chemistry letters. 27(4)
Publication Year :
2016

Abstract

Taking into account that multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment and as a continuation of our efforts to overcome this problem we report the evaluation of one cyclic selenoanhydride (1) and ten selenoesters (2-11) in MDR human colon adenocarcinoma Colo 320 cell line. The most potent derivatives (1, 9-11) inhibited the ABCB1 efflux pump much stronger than the reference compound verapamil. Particularly, the best one (9) was 4-fold more potent than verapamil at a 10-fold lower concentration. Furthermore, the evaluated derivatives exerted a potent and selective cytotoxic activity. In addition, they were strong apoptosis inducers as the four derivatives triggered apoptotic events in a 64-72% of the examined MDR Colo 320 human adenocarcinoma cells.

Details

ISSN :
14643405
Volume :
27
Issue :
4
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry letters
Accession number :
edsair.doi.dedup.....644b17a5033757ede5dd982eed861f85