New Fluoro- and Trifluoromethyl-Substituted Trimethoxychalcones as Anticancer Agents: Synthesis, Bio-evaluation, and Computational Studies

We designed and synthesized a novel series of trimethoxy chalcones with CF3 or F substituents at various positions of ring B, characterized using IR, NMR spectral data, and elemental analyses, based on the fact that methoxy and fluoro-substituted chalcones are included in the literature as a pharmacophore due to their anticancer activities. All compounds (12-21) were tested for cytotoxicity against A549, HEPG2, MCF7, and normal mouse fibroblasts (L929) using the XTT assay. The most active compound, 13, was also shown to induce MCF7 cell cycle arrest at the G0/G1 phase, indicating that they exert their antitumor potency via MCF7 cell apoptosis. The mechanisms involved in apoptotic cell death induced by compound 13 were also investigated to see if apoptotic proteins such as Bax, Bcl-2, and p53 were involved. In addition, the compounds with the strongest apoptotic effects against human EGFR and VEGFR-2 receptors were studied in silico. Finally, methoxy and fluoro-substituted chalcones derivatives have been shown to have potent anticancer properties.

Automated summary

A novel series of trimethoxy chalcones with CF3 or F substituents at different positions of ring B were designed and synthesized. These compounds were characterized using IR, NMR spectral data, and elemental analyses. Their cytotoxicity against A549, HEPG2, MCF7, and L929 cells was evaluated, and compound 13 showed the highest activity and induced cell cycle arrest at the G0/G1 phase in MCF7 cells. The apoptotic mechanisms of compound 13 involving Bax, Bcl-2, and p53 were also investigated, along with their effects on human EGFR and VEGFR-2 receptors.