title: Selenium-containing chrysin and quercetin derivatives: attractive scaffolds for cancer therapy.
abstract: Selenium-containing chrysin (SeChry) and 3,7,3',4'-tetramethylquercetin (SePQue) derivatives were synthesized by a microwave-based methodology. In addition to their improvement in terms of DPPH scavenging and potential GPx-like activities, when tested in a panel of cancer cell lines both selenium-derivatives revealed consistently to be more cytotoxic when compared with their oxo and thio-analogues, evidencing the key role of selenocabonyl moiety for these activities. In particular, SeChry elicited a noteworthy cytotoxic activity with mean IC50 values 18- and 3-fold lower than those observed for chrysin and cisplatin, respectively. Additionally, these seleno-derivatives evidenced an ability to overcome cisplatin and multidrug resistance. Notably, a differential behavior toward malignant and nonmalignant cells was observed for SeChry and SePQue, exhibiting higher selectivity indexes when compared with the chalcogen-derivatives and cisplatin. Our preliminary investigation on the mechanism of cytotoxicity of SeChry and SePQue in MCF-7 human mammary cancer cells demonstrated their capacity to efficiently suppress the clonal expansion along with their ability to hamper TrxR activity leading to apoptotic cell death.
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: Inês L
authors.initials: IL
authors.lastname: Martins
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Charneira
authors.affiliation: ‡Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: João L
authors.initials: JL
authors.lastname: Ferreira da Silva
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: Gonçalo C
authors.initials: GC
authors.lastname: Justino
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Telo
authors.affiliation: §LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Abel J S C
authors.initials: AJ
authors.lastname: Vieira
authors.affiliation: ‡Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa 1049-001, Portugal.
authors.forename: Alexandra M M
authors.initials: AM
authors.lastname: Antunes
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002945:Cisplatin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D015394:Molecular Structure; D011794:Quercetin / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D016166:Free Radical Scavengers; C043561:chrysin; D011794:Quercetin; D012643:Selenium; D002945:Cisplatin