Antiproliferative Activity of -Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar) and lenvatinib (Lenvima) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of -acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the derivative was the most effective. Further, we demonstrated that treatment induced downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as and , , and . In addition, significantly reduced and expression in HCC cells. Our findings indicate that is a promising prototype for further in vivo studies.