Paloma Begines1, Ana Oliete1, Óscar López1, Inés Maya1, Gabriela B Plata2, José M Padrón2, José G Fernández-Bolaños1. 1. Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla. Apartado 1203, E-41071, Seville, Spain. 2. BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González' (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, E-38206, La Laguna, Spain.
Abstract
AIM: The increasing number of cancer cases has stimulated researchers to seek for novel approaches. We have combined two bioactive moieties: a polyphenolic scaffold and an organoselenium motif. Four different families (isothiocyanates/thioureas, and their selenium isosters) derived from dopamine, (±)-norepinephrine and R-epinephrine were accessed. RESULTS: Heterocumulenes derived from dopamine and β-O-methylnoradrenaline were strong antiproliferative agents (GI50<10 μM). Selenoureas derived from β-O-methylnoradrenaline bearing electron-withdrawing groups (halogen, -NO2, -Ph) on the phenyl ring, were also strong antiproliferative agents, besides exhibiting good antiradical and glutathione peroxidase-like activities. Up to a 14-fold increased activity was achieved compared with classical chemotherapeutic agents, exhibiting also different mechanisms of action (cell cycle assays). Redox analysis on HeLa cells suggested an increase of ROS levels after the incubation period. CONCLUSION: the combination of organoselenium and phenolic moieties might provide valuable lead compounds with relevant antiproliferative properties.
AIM: The increasing number of cancer cases has stimulated researchers to seek for novel approaches. We have combined two bioactive moieties: a polyphenolic scaffold and an organoselenium motif. Four different families (isothiocyanates/thioureas, and their selenium isosters) derived from dopamine, (±)-norepinephrine and R-epinephrine were accessed. RESULTS: Heterocumulenes derived from dopamine and β-O-methylnoradrenaline were strong antiproliferative agents (GI50<10 μM). Selenoureas derived from β-O-methylnoradrenaline bearing electron-withdrawing groups (halogen, -NO2, -Ph) on the phenyl ring, were also strong antiproliferative agents, besides exhibiting good antiradical and glutathione peroxidase-like activities. Up to a 14-fold increased activity was achieved compared with classical chemotherapeutic agents, exhibiting also different mechanisms of action (cell cycle assays). Redox analysis on HeLa cells suggested an increase of ROS levels after the incubation period. CONCLUSION: the combination of organoselenium and phenolic moieties might provide valuable lead compounds with relevant antiproliferative properties.
Authors: Alexandra Ibáñez-Escribano; Cristina Fonseca-Berzal; Mónica Martínez-Montiel; Manuel Álvarez-Márquez; María Gómez-Núñez; Manuel Lacueva-Arnedo; Teresa Espinosa-Buitrago; Tania Martín-Pérez; José Antonio Escario; Penélope Merino-Montiel; Sara Montiel-Smith; Alicia Gómez-Barrio; Óscar López; José G Fernández-Bolaños Journal: J Enzyme Inhib Med Chem Date: 2022-12 Impact factor: 5.051
Authors: Elena M Sánchez-Fernández; Raquel García-Hernández; Francisco Gamarro; Ana I Arroba; Manuel Aguilar-Diosdado; José M Padrón; José M García Fernández; Carmen Ortiz Mellet Journal: Molecules Date: 2021-12-11 Impact factor: 4.411