Synthesis, Characterization and Biological Evaluation of New Enamide Fluorinated‐Schiff Base Derivatives as Potential Cytotoxic and Apoptosis‐Inducing Agents

Abstract

AbstractIn search for new anticancer candidates, a new series of enamide fluorinated‐Schiff base derivatives were synthesized and confirmed by spectroscopic techniques as well as elemental microanalyses. The newly prepared compounds were evaluated for their cytotoxic activity on MCF‐7 breast adenocarcinoma cell line. The benzaldehyde Schiff base and furfural Schiff base derivatives (IC50=3.67±0.15 and 2.06±0.08 μM, respectively) were found to be the most potent molecules of all the tested derivatives against the MCF‐7 cancer cells. Additionally, the furfural Schiff base compound was more potent than colchicine by 1.74‐fold, while benzaldehyde Schiff base compound was nearly equipotent with colchicine as standard drug. In addition to tubulin inhibition activity, enamide‐furfural Schiff base molecule caused cell cycle arrest in MCF‐7 cells at the G2/M phase (2.62‐fold more than control MCF‐7) and induced apoptotic death (48.97‐fold compared to untreated MCF‐7 control) as indicated by FACS analysis. Furthermore, apoptotic studies conducted by enamide‐furfural Schiff base derivative were accomplished by downregulation of mitochondrial membrane potential by 1.56‐fold relative to control untreated cells.