Synthesis of oxazoline hydroxamates α,β-unsaturated: Cytotoxic evaluation and inhibitory activity in vitro of histone deacetylases

A series of 28 molecules were synthesized: ten β-hydroxyamides, nine oxazoline esters, and nine oxazoline hydroxamates. Of these compounds, 16 represent new molecules. All synthesized compounds were evaluated against four cancer cell lines (MCF7, PC-3, NCI-H460, and HT-29) and one normal cell line (Vero). The results demonstrated that compound 4 h exhibited the highest activity, with an IC 50 of 7.65 μg/mL (24.67 μM) in PC-3 cells, which were determined to be the most sensitive cell line to the compounds. Because of this, the PC-3 cell line, as well as the Vero cell line, was chosen to evaluate the eventual inhibition of the HDAC enzyme by the most active oxazoline and hydroxamate ( 4 h and 5f , respectively) and to be able to analyze the possible mechanism of action exerted by these compounds. The inhibitory activity of HDAC produced by 4 h and 5f in PC-3 cells was found to be greater than that shown by the reference drug Vorinostat. In contrast, in Vero cells, the reference drug showed greater inhibitory activity than compounds 4 h and 5 f . These results suggest that compounds 4 h and 5f have greater selectivity towards HDAC cancer cells compared to normal growth cells; however, with less anticancer activity in vitro . • XtalFluor-E proved to be a good alternative for obtaining and oxazolines • In general, electron-withdrawing groups increase cytotoxic activity • Hydroxamates had promising cytotoxic activity but oxazoline esters were more active • 4 h and 5f had higher inhibition of HDAC in PC-3 cells compared to Vorinostat • In Vero cells, 4 h and 5f showed lesser suppression of HDAC activity than Vorinostat