Anti-hepatocellular carcinoma activities of novel hydrazone derivatives via downregulation of interleukin-6

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related morbidity worldwide. Sorafenib is a first-line drug for the treatment of HCC, however, it is reported to cause serious adverse effects and may lead to resistance in many patients. In this study, 20 hydrazone derivatives incorporating triazoles, pyrazolone, pyrrole, pyrrolidine, imidazoline, quinazoline, and oxadiazine moieties were designed, synthesized, and characterized. In addition to molecular docking and in silico ADME study, the cytotoxic activity of the synthesized compounds was evaluated against the human hepatocellular cancer cell line (HepG2) and liver mesenchymal stem cells as a normal cell line. The antitumor activities of the derivatives against sorafenib were compared. Of the 20 synthesized compounds, compound 16 demonstrated potential as a potent anti-HCC drug candidate through downregulation of interleukin 6 which reduces inflammation and tumorigenesis with a strong binding interaction and bioavailability.