Synthesis, Characterization, Antioxidant, and Anticancer Activity against Colon Cancer Cells of Some Cinnamaldehyde-Based Chalcone Derivatives

Abstract

The purpose of the current investigation was to produce cinammaldehyde-based chalcone derivatives (<b>3a</b>-<b>k</b>) to evaluate their potential effectiveness as antioxidant and inhibitory agents versus human Caco-2 cancer cells. The findings obtained using the DPPH assay showed that compound <b>3e</b> had the highest effective antioxidant activity with the best IC₅₀ value compared with the other compounds. Moreover, the cytotoxic findings revealed that compound <b>3e</b> was the best compound for inhibiting Caco-2 development in contrast to all other produced derivatives, with the lowest IC₅₀ concentration (32.19 ± 3.92 µM), and it also had no detrimental effects on healthy human lung cells (wi38 cells). Exposure of Caco-2 cells with this IC₅₀ value of compound <b>3e</b> resulted in a substantial rise in the number of early and late cells that are apoptotic with a significant comet nucleus when compared with control cells employing the annexin V/PI and comet evaluations, respectively. Furthermore, qRT-PCR and ELISA examinations indicated that compound <b>3e</b> significantly altered the expression of genes and their relative proteins related to apoptosis in the treated Caco-2 cells, thus significantly inhibiting Caco-2 growth through activating Caspase-3 via an intrinsic apoptotic pathway. As a result, compound <b>3e</b> could serve as an effective therapy for human colon cancer.