title: Novel structural insights for imidoselenocarbamates with antitumoral activity related to their ability to generate methylselenol.
abstract: In the search for molecules with potential antiangiogenic activity we found that several imidoselenocarbamate derivatives, which have pro-apoptotic and antiproliferative activities, under hypoxic conditions release methylselenol, a volatile and highly reactive gas that was considered to be responsible for the observed biological activity. The kinetic for the liberation of methylselenol is highly dependent on the nature of the overall structure and correlate with their proven pro-apoptotic activity in lung cancer cell line H157. The preliminary structure-activity relationships allow us to select as the basic structural element a scaffold constructed with an imidoselenocarbamate fragment decorated with a methyl residue on the Se central atom and two heteroaromatic lateral rings. These imidoselenocarbamate derivatives may be of interest both for their antitumoral activities and because they have a structure that can be considered as a template for the design of new derivatives with apoptotic activity. This activity is related to the controlled delivery of methylselenol and makes this an interesting approach to develop new antitumoral agents.
authors.affiliation: Sección de Modelización Molecular, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain. mfont@unav.es
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.forename: Alicia
authors.initials: A
authors.lastname: Zuazo
authors.forename: Elena
authors.initials: E
authors.lastname: Ansó
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.forename: Juan-Antonio
authors.initials: JA
authors.lastname: Palop
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Martínez-Irujo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D016566:Organoselenium Compounds; C019003:methaneselenol; D000432:Methanol