title: Synthesis and antiproliferative activity of novel methylselenocarbamates.
abstract: A series of new aliphatic, aromatic and heteroaromatic carbamate derivatives containing a methylseleno moiety were synthesized and evaluated in vitro for their cytotoxic activity against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), K-562 (lymphocytic 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 are highly cytotoxic with GI50 values below 10 μM in every tested tumour cell line. Based on its cytotoxic parameters, selectivity index and ADME profile, the biological activity of compound 2, the propyl derivative, was further analysed in CCRF-CEM and HTB-54 cells. Results showed that this compound is able to induce apoptosis in a time- and dose-dependent manner. Involvement of caspases in cell death induction by 2 was detected. Besides, compound 2 was also able to induce cell cycle arrest at G0/G1 in CCRF-CEM cells and at G2/M in HTB-54 cells.
authors.affiliation: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Romano
authors.affiliation: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Pública de Navarra, Avda. Barañain s/n, E-31008 Pamplona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Encío
authors.affiliation: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain. Electronic address: jpalop@unav.es.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Palop
authors.affiliation: Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds
keywords: Apoptosis; Carbamate; Cell cycle arrest; Cytotoxicity; Methylseleno