title: Synthesis and biological activity of 6-selenocaffeine: potential modulator of chemotherapeutic drugs in breast cancer cells.
abstract: 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.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, 1049-001 Lisboa, Portugal.
authors.forename: Inês L
authors.initials: IL
authors.lastname: Martins
authors.forename: Joana P
authors.initials: JP
authors.lastname: Miranda
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Oliveira
authors.forename: Ana S
authors.initials: AS
authors.lastname: Fernandes
authors.forename: Sandrina
authors.initials: S
authors.lastname: Gonçalves
authors.forename: Alexandra M M
authors.initials: AM
authors.lastname: Antunes
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002110:Caffeine / Q000819:agonists / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000819:agonists / Q000494:pharmacology; D054313:Drug Agonism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000819:agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000077150:Oxaliplatin
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D009944:Organoplatinum Compounds; D016566:Organoselenium Compounds; D000077150:Oxaliplatin; D002110:Caffeine; D004317:Doxorubicin