Artículo de revista
Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation
Fecha
2010Registro en:
Bioorganic and Medicinal Chemistry, Volumen 18, Issue 12, 2018, Pages 4433-4440
09680896
10.1016/j.bmc.2010.04.074
Autor
Lavaggi, María Laura
Cabrera, Mauricio
Aravena, María de los Ángeles
Olea Azar, Claudio
López de Ceráin, Adela
Monge, Antonio
Pachón, Gisela
Cascante, Marta
Bruno, Ana María
Pietrasanta, Lía I.
González, Mercedes
Cerecetto, Hugo
Institución
Resumen
Phenazine 5,10-dioxides are prodrugs for antitumor therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here we investigate the expanded system benzo[a]phenazine 7,12-dioxides as selective hypoxic cytotoxin-scaffold. The clonogenic survival of V79 cells on aerobic and anaerobic conditions, conduct us to study antiproliferative activity on Caco-2 tumoral cells in normoxia. Electrochemical, DNA-interaction and DNA-damage studies were performed to establish the mode of action. The results demonstrated the potential biological properties of the studied scaffold being derivatives 6-10 structural hits for further chemical-modifications to become into therapeutics for solid tumors. Compounds 6 and 8 with cytotoxicity against V79 cells in both conditions (aerobia and anaerobia) were also cytotoxic against Caco-2 tumoral cells in aerobiosis. © 2010 Elsevier Ltd. All rights reserved.