Synthesis, characterization, and antiproliferative evaluation of novel sorafenib analogs for the treatment of hepatocellular carcinoma

Cancer is a disease triggered by an uncontrolled proliferation of a cluster of cells, typically originating from a single cell. Sorafenib, a widely utilized pharmaceutical, has limitations in clinical use due to pharmacokinetic challenges and the development of resistance mechanisms. This investigation aimed to synthesize new sorafenib analogs and evaluated their activity against HepG2 cell lines, specifically targeting hepatocellular carcinoma (HCC). Seven sorafenib analogs were synthesized and identified by Fourier-transform infrared spectroscopy and 1H-NMR spectra. Cytotoxicity of the analogs was assessed on the human HepG2 cancer cell line by (3-(4, 5-dimethylthazolk-2-yl)-2, 5-diphenyl tetrazolium bromide) colorimetric assay. Results revealed that among the studied compounds, 4b exhibited the most pronounced cytotoxicity against cancer cells, surpassing even the efficacy of sorafenib. This suggested that small substitutions on the NH moiety play a crucial role in the activity against the human HepG2 liver cancer cell line. These findings provide valuable insights for the development of potential anticancer-targeting HCC.