Antitumoral effect of phenazine N5,N10-diioxide derivatives on Caco-2 cells

ANTINEOPLASICOS

2008

BIBLIOGRAFÍA NACIONAL QUÍMICA

We studied the in vitro antitumoral effect of a series of phenazine di-N-oxide derivatives, named 2-chloroacetylamino-7(8)-nitrophenazine N5,N10-dioxide (1), 2-amino-7(8)-(1,3-dioxol-2-yl)phenazine N5,N10-dioxide (2), 2-chloroacetylamino-7(8)-(1,3-dioxol-2-yl)phenazine N5,N10-dioxide (3), and 2-amino-7(8)-methoxyphenazine N5,N10-dioxide (4), on Caco-2 cells. These phenazine N5,N10-dioxide derivatives belong to our in-house chemical library. The products were selected according to their stereoelectronic characteristics and taking into account their differential cytotoxicity against V79 cells. Human colorectal adenocarcinoma cell line Caco-2 was used to study the cell growth inhibition capacity of these compounds, their capacity of altering the cell cycle and possible induction of apoptosis, DNA fragmentation, and genotoxic damage. The IC50 after 24 h of incubation was lower for 1, 2, and 3 (4.8, 46.8, and 8.2 μM, respectively) than for 4 (474.7 μM). Compound 1 induced arrest in the G2/M phase at 24 and 48 h of treatment and apoptosis at the highest doses at 24 h of treatment. These facts were corroborated with caspase 3, caspase 9, and cytochrome c activation and DNA fragmentation at 24 h of treatment. The derivatives studied induced neither significant single strand breaks nor oxidative damage at the different studied times.We concluded that among the series of N5,N10-dioxide phenazine derivatives analyzed, 1, which contains a nitro moiety and a chloroacetamide group, is the most promising as an antitumoral compound.

Chemical Research in Toxicology v. 21, no. 8, 2008. -- p. 1578-1585

ACSPublications

2008

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Inglés

Artículo

DOI: 10.1021/tx800032k