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

Molecules

Inês L. Martins²  Joana P. Miranda³  Nuno G. Oliveira³  Ana S. Fernandes¹  Sandrina Gon๺lves³ 

[1] CBIOS, Universidade Lusófona de Humanidades e Tecnologias, 1749-024 Lisboa, Portugal; E-Mail:;Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, 1049-001 Lisboa, Portugal; E-Mail:;Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; E-Mails:

关键词: organoselenium compounds;    caffeine;    modulator of the cytoxicity;    oxaliplatin;    doxorubicin;    cancer therapy;   

DOI  :  10.3390/molecules18055251

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.