Cytotoxic effects of some 1-[(benzofuran-2-yl)-phenylmethyl]-imidazoles on MCF-7 and Hela cell lines

Abstract

Aromatase inhibitors have been used as a second line therapy after tamoxifen, in estrogen-receptor positive (ER+) women to reduce estrogen concentration in plasma and breast tumors. It has been shown that benzofuran(phenylmethyl)imidazoles are potent aromatase inhibitors at nano-molar concentrations, about 1000 times more potent than aminoglutetimide. In this study, cytotoxic activity of some of these potent aromatase inhibitors (compounds 1-6) on MCF-7 and Hela cell lines were evaluated. MCF-7 and Hela cells were cultured on RPMI medium and the cells obtained after the third generation were used in this study. The cytotoxic activity of the compounds was first screened at 20 and 100 µM. The IC50 values were then determined, using MTT method. Briefly, after 24 h incubation of the cells, the compounds, doxorubicine and the medium were added to the cells and incubated for further 48 h (37 oC, 5% CO2). The MTT solution was then added and the absorbance was measured by ELISA plate reader at 540 nm after 4 h incubation. The results indicated that the IC50 values for compounds 1-6 were around 35-80 µM for MCF-7 and 47-85 µM for Hela cells. Compound 5, the 4-chloro derivative, showed almost the highest toxicity on both cell lines. i.e. IC50s were 35 µM and 55 µM for MCF-7 and Hela cells, respectively. The cytotoxic activity could be in part due to the aromatase inhibition but other mechanisms like DNA degradation may also be involved.