Study of benzo[a]phenazine 7,12-dioxide as selective hypoxic cytotoxin-scaffold. Identification of aerobic-antitumoral activity through DNA fragmentation
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.
Lavaggi, Maria Laura,Cabrera, Mauricio,Aravena, Maria de los Angeles,Olea-Azar, Claudio,Lopez de Cerain, Adela,Monge, Antonio,Pachon, Gisela,Cascante, Marta,Bruno, Ana Maria,Pietrasanta, Lia I.,Gonzalez, Mercedes,Cerecetto, Hugo
A new Route for the Synthesis of Phenazine Di-N-Oxides
Several phenazine 5,10-dioxides (7a-d) were prepared by the reaction of 2-methyl-3-acetylquinoxaline 1,4-dioxide (2) with different aromatic aldehydes or by direct cyclization of the quinoxaline cinnamoyl derivatives 3 in basic medium.In addition, the phe
El-Halim, M. S. Abd,El-Ahl, A. S.,Etman, H. A.,Ali, M. M.,Fouda, A.,Fadda, A. A.
p. 1217 - 1224
(2007/10/03)
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