A novel trifluoromethyl 2-phosphonopyrrole analogue inhibits human cancer cell migration and growth by cell cycle arrest at G1 phase and apoptosis.

ABSTRACT

Pyrroles, an important class of heterocyclic compounds found in naturally occurring products, represent an interesting biologically active scaffold for drug design. Recently we have synthetized a series of five new fluorinated pyrrole derivatives for potential anticancer applications. All new compounds contain a trifluoromethyl and N-benzyl group, but they are different from each other by bearing a phenyl, ethoxycarbonyl or carboxylic moiety, with two of them possessing an additional phosphonyl function. The aim of this study was to evaluate anticancer activity of the new compounds in human lung and breast cancer cells. We found that compound 3, bearing a phosphonyl and phenyl group, was the most effective in attenuating growth of A549 and MCF-7 cells in a dose dependent manner with IC50 36.5 µM ± 1.80 and 27.9 µM ± 1.68, respectively. Compound 3 inhibited cancer cell proliferation by cell cycle arrest at G1 phase as detected by flow cytometry analysis. Furthermore, compound 3 induced apoptosis of A549 cells by activation of caspase-3. Cancer cell migration rate was significantly inhibited when A549 and MCF-7 cells were cultured in the presence of the compound. These results demonstrate that a novel trifluoromethyl-functionalized phosphonopyrrole with a phenyl group might be a promising pyrrole analogue with anticancer potential.