Design, Synthesis, and In Vitro Antiproliferative Screening of New Hydrazone Derivatives Containing cis-(4-Chlorostyryl) Amide Moiety

Abstract

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.

Special Issue: Asymmetry and Symmetry in Organic Chemistry

“…In the study [3], a series of novel hydrazone derivatives containing cis-(4-chlorostyryl) amide was synthesized and cytotoxic activity against a breast cancer cell line was evaluated. Some of those derivatives exhibited promising cytotoxic activities with IC 50 values between 2.19-4.37 µM.…”

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

“…Numerous compounds that resemble CA-4 have been created and studied as possible anticancer drugs. − Two aromatic rings are connected by a different moiety, such as olefins, enamides, or heterocyclic functions, to form CA-4 analogues. − According to SAR studies, ring A’s trimethoxy group is a crucial pharmacophoric site for tubulin, whereas ring B’s halogenated phenyl group preserves the antitubulin activity. , The maintenance of tissue growth and homeostasis depends heavily on apoptosis, a critical cellular function. , Apoptotic pathway regulation issues have been connected to a variety of diseases, including cancer . In order to find effective cancer treatments, it has become common practice to design and prepare novel chemotherapeutic chemicals that are capable of triggering apoptotic death. − …”

“… 23 In order to find effective cancer treatments, it has become common practice to design and prepare novel chemotherapeutic chemicals that are capable of triggering apoptotic death. 24 − 26 …”