Dipeptidyl nitrile derivatives as bioactive compounds against MIA PaCa-2 pancreatic cancer lineage

Pancreatic cancer is still a deadly disease, with a high occurrence of metastasis and infective treatment. Therefore, the work analyzed the activity of synthesized dipeptidyl nitrile derivatives using pancreatic cancer lineage (MIA PaCa-2)1, by viability assay, migration, colony formation, and inhibition of cell cysteine protease activity. The homologous series of (S)-N-(1-((1-cyanocyclopropyl)amino)-1-oxo-3-henylpropan-2-yl)benzamide was assayed against MIA PaCa-2 cells cultured in standard conditions with DMEM medium. It was found that Neq0709 and Neq0712 inhibited cysteine protease activity, while just Neq0709 led to colony reduction above the 50% threshold. All compounds were inactive in the wound healing assay. In short, the compound containing the chlorine atom in the o-position was active in two of the three assays (Neq0709), while the m-CH3 derivative (Neq0712) only inhibited proteolysis. Other chlorine-containing derivatives (meta and para) were inactive. These results demonstrate that the chlorine in ortho-position is essential for the bioactivity.