title: Structural variations on antitumour agents derived from bisacylimidoselenocarbamate. A proposal for structure-activity relationships based on the analysis of conformational behaviour.
abstract: A molecular modelling study has been carried out on a previously reported series of symmetrically substituted bisacylimidoselenocarbamate (BSeC) derivatives that show remarkable antitumour activity in vitro against a panel of human tumour cell lines. These derivatives can be considered as a central scaffold constructed around a methyl carbamimidoselenoate nucleus in which two heteroarylacyl fragments are located on the scaffold nitrogen atoms, thus forming the different BSeCs. The results reveal that the nature of the selected heteroaryl ring has a marked influence on the antiproliferative activity of the compounds and this can be related, as a first approximation, to the ability to release methylselenol (MeSeH), a compound that, according to our initial hypothesis, is ultimately responsible for the antitumour activity of the compounds under investigation. The release of MeSeH from the active BSeCs has been confirmed by means of Head Space Gas Chromatography Mass Spectrometry techniques. The data that support this connection include the topography of the molecules, the conformational behaviour of the compounds, which influences the accessibility of the hydrolysis point, the interaction map obtained for an O2H type probe, and the location and energy of the HOMO/LUMO orbitals.
authors.affiliation: Sección de Modelización Molecular, Facultad de Farmacia, Departamento de Química Orgánica y Farmacéutica, Universidad de Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain. mfont@unav.es
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.forename: Elena
authors.initials: E
authors.lastname: Lizarraga
authors.forename: Elena
authors.initials: E
authors.lastname: Ibáñez
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.forename: Juan A
authors.initials: JA
authors.lastname: Palop
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D016566:Organoselenium Compounds; C586654:bisacylimidoselenocarbamate
keywords: Antiproliferative; Bisacylimidoselenocarbamate; Methylselenol release