title: Topological and quantum molecular descriptors as effective tools for analyzing cytotoxic activity achieved by a series of (diselanediyldibenzene-4,1-diylnide)biscarbamate derivatives.
abstract: A molecular modeling study has been carried out on a previously reported series of (diselanediyldibenzene-4,1-diylnide)biscarbamate derivatives that show cytotoxic and antiproliferative in vitro activity against MCF-7 human cell line; radical scavenging properties were also confirmed when these compounds were tested for their ability to scavenge DPPH and ABTS radicals. The data obtained allowed us to classify the compounds into two different groups: (a) aliphatic carbamates for which the activity could be related with a first nucleophilic attack (mediated by H2O, for example) on the selenium atoms of the central scaffold, followed by the release of the alkyl N-(4-selanylphenyl) and N-(4-selenenophenyl)carbamate moieties. Then, a second nucleophilic attack on the carbamate moiety, to yield 4-aminobenzeneselenol and 4-selenenoaniline respectively, which can ultimately be responsible for the activity of the compounds; (b) aromatic carbamates, for which we propose a preferred nucleophilic attack on the carbamate moiety, yielding 4-[(4-aminophenyl)diselanyl]aniline, the common structural fragment for this series, for which we have previously demonstrated its cytotoxic profile. Then, selenium atoms of the central fragment may later undergo a new nucleophilic attack, to yield 4-selenenoaniline and 4-aminobenzeneselenol. The phenolic moieties released in this process may also have a synergistic cytotoxic and redox activity. The data that support this connection include the conformational behavior and the molecular topography of the derivatives which can influence the accessibility of the hydrolysis points, and some quantum descriptors (bond order, atomic charges, total valences, ionization potential, electron affinity, HOMO 0 and LUMO 0 location, etc.) that have been related to the biological activity of the compounds.
authors.affiliation: University of Navarra, School of Pharmacy and Nutrition, Dpto de Química Orgánica y Farmacéutica, Sección de Modelización Molecular, Irunlarrea, 1, Pamplona, E-31008, Spain; IdISNA, Instituto de Investigación Sanitaria de Navarra, Recinto del Complejo Hospitalario de Navarra, Irunlarrea 3, Pamplona, E-31008, Spain. Electronic address: mfont@unav.es.
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.affiliation: IdISNA, Instituto de Investigación Sanitaria de Navarra, Recinto del Complejo Hospitalario de Navarra, Irunlarrea 3, Pamplona, E-31008, Spain; University of Navarra, School of Pharmacy and Nutrition, Dpto de Química Orgánica y Farmacéutica, Sección de Síntesis, Navarra, Irunlarrea, 1, Pamplona, E-31008, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.affiliation: IdISNA, Instituto de Investigación Sanitaria de Navarra, Recinto del Complejo Hospitalario de Navarra, Irunlarrea 3, Pamplona, E-31008, Spain; University of Navarra, School of Pharmacy and Nutrition, Dpto de Química Orgánica y Farmacéutica, Sección de Síntesis, Navarra, Irunlarrea, 1, Pamplona, E-31008, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.affiliation: University of Navarra, School of Pharmacy and Nutrition, Dpto de Química Orgánica y Farmacéutica, Sección de Síntesis, Navarra, Irunlarrea, 1, Pamplona, E-31008, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Palop
mesh_terms: D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D002244:Carbon / Q000032:analysis; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D011789:Quantum Theory; D012643:Selenium / Q000032:analysis
chemical_list: D002219:Carbamates; D002244:Carbon; D012643:Selenium
keywords: Cytotoxicity; Diselenides; Quantum descriptors; Redox; Topological descriptors