Hydrazones are regarded as a distinctive category of organic compounds because of their tremendous characteristics and potential uses in analytical, chemical, and medicinal chemistry. In the present study, a new series of Hydrazone Derivatives bearing cis-(4-chlorostyryl) amide moiety were designed and synthesized. In vitro cytotoxicity screening showed that compounds 3i, 3l, 3m, and 3n revealed potent anticancer activity against MCF-7 cancer cell line with IC50 values between 2.19–4.37 μM compared with Staurosporin as a reference compound. The antiproliferative activity of these compounds appears to be correlated well with their ability to inhibit the VEGFR-2 kinase enzyme. Activation of the damage response pathway leads to cellular cycle arrest at the G1 phase. Fluorochrome Annexin V/PI staining indicated that cell death proceeds through the apoptotic pathway mechanism. The mechanistic pathway was confirmed by a significant increase in the level of active caspase 9 compared with control untreated MCF-7 cells.
