Author/Authors :
Mar?a Laura Lavaggi، نويسنده , , Mauricio Cabrera، نويسنده , , Mar?a de los ?ngeles Aravena، نويسنده , , Claudio Olea-Azar، نويسنده , , Adela L?pez de Cer?in، نويسنده , , Antonio Monge، نويسنده , , Gisela Pach?n، نويسنده , , Marta Cascante، نويسنده , , Ana Mar?a Bruno، نويسنده , , L?a I. Pietrasanta، نويسنده , , Mercedes Gonzalez-Wangüemert، نويسنده , , Hugo Cerecetto، نويسنده ,
Abstract :
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.
