Synthesis and Biological Activity of 6-Selenocaffeine: Potential Modulator of Chemotherapeutic Drugs in Breast Cancer Cells

• Main Authors: Inês L. Martins, Joana P. Miranda, Nuno G. Oliveira, Ana S. Fernandes, Sandrina Gonçalves, Alexandra M. M. Antunes
• Format: Article
• Language: English
• Published: MDPI AG 2013-05-01
• Series: Molecules
• Subjects: organoselenium compounds; caffeine; modulator of the cytoxicity; oxaliplatin; doxorubicin; cancer therapy
• Online Access: http://www.mdpi.com/1420-3049/18/5/5251

We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild antioxidant activity for 6-selenocaffeine, contrasting with caffeine, that exhibited no antioxidant activity under the same experimental conditions. Interestingly, whereas 6-selenocaffeine has revealed to have a low cytotoxic potential in both MCF10A and MCF-7 breast cells (24 h, up to 100 µM, MTT assay), a differential effect was observed when used in combination with the anticancer agents doxorubicin and oxaliplatin in MCF-7 breast cancer cells. The co-treatment of doxorubicin (1 µM) and 6-selenocaffeine (100 µM) resulted in a slight decrease in cellular viability when compared to doxorubicin (1 µM) alone. Conversely, the seleno-caffeine derivative at the same concentration markedly increased the viability of oxaliplatin (100 µM)-treated cells (p < 0.01). Overall, this work highlights an emerging methodology to synthesize organoselenium compounds and points out the differential roles of 6-selenocaffeine in the modulation of the cytotoxicity of anticancer agents.