artículo
Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents
Fecha
2010Registro en:
10.1016/j.ejmech.2010.10.006
1768-3254
0223-5234
MEDLINE:20980080
WOS:000285485000060
Autor
Benites, Julio
Valderrama, Jaime A.
Bettega, Karina
Pedrosa, Rozangela Curi
Buc Calderon, Pedro
Verrax, Julien
Institución
Resumen
Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells) and healthy fibroblasts (BALB/3T3) were assessed in vitro using the MTT reduction assay 48 h after drug exposure. SAR analysis of the aminonaphthoquinone series showed that insertion of a chlorine atom in the acceptor quinone nucleus and/or insertion of a methyl group at the nitrogen atom of the donor phenylamino group induced significant changes in cytotoxic activity. Quinones 7 and 9, which exhibited the highest selective indexes (5.73 and 6.29, respectively), were further characterized using the following assays: Colony formation, caspase-3 activity, and ATP content. The results showed that aminoquinone 7 strongly influenced ATP levels and impaired the proliferative capacity of T24 cells without activating caspase-3. (C) 2010 Elsevier Masson SAS. All rights reserved.