Antitumoral Effect of Phenazine N5,N10-Dioxide Derivatives on Caco-2 Cells

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 ...