title: In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates.
abstract: Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.
authors: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain.
authors: Beatriz
authors: B
authors: Romano
authors: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain.
authors: Daniel
authors: D
authors: Plano
authors: Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain; Departamento de Ciencias de la Salud, Universidad Pública de Navarra, Avda. Barañain s/n, E-31008 Pamplona, Spain.
authors: Ignacio
authors: I
authors: Encío
authors: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain. Electronic address: jpalop@unav.es.
authors: Juan Antonio
authors: JA
authors: Palop
authors: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain.
authors: Carmen
authors: C
authors: Sanmartín
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003485:Cyanates / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D003485:Cyanates; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D018036:Selenium Compounds; C053721:selenocyanic acid
keywords: ABTS(+); Carbamate; Cytotoxicity; DPPH; GPx; Radical scavenging; Selenium