Evaluation of Anticancer Activity of Novel Sulfanyl-Substituted Hydrazone Compounds in Hepatocellular Carcinoma: In Vitro, In Silico, and In Ovo Studies

Hepatocellular carcinoma is one of the hardest-to-treat cancer types, although some recent developments have been made. Therefore, the discovery of new treatment options is still desperately desired. In this study, some novel sulfanyl-substituted hydrazone compounds <b>2a-2h</b> were synthesized and characterized using spectroscopic techniques (¹H NMR, ¹³C NMR, IR, and HRMS). Then, hydrazone compounds were tested on four different cancer types (lung, hepatocellular, breast, and colon carcinoma) and one nonmalignant cell line. Among these hydrazone compounds and tested cancer types, compound <b>2c</b> resulted in a satisfactory antigrowth effect against hepatocellular carcinoma, the HepG2 cell line. Further, in ovo antitumor and antiangiogenic assays were also performed together with the in silico calculations employed by target predictions of compound <b>2c</b> by a tool called Way2Drug and then followed by binding affinity calculations to those targets by AutoDock Vina. The range of binding scores of compound <b>2c</b> was calculated between -4 and -8.6 kcal/mol for those targets that were suggested to be involved in a local protein-protein interaction clustering on base excision repair and DNA topological change. It has been found that compound <b>2c</b> might deserve further attention (e.g., animal studies for proof-of-concept) as a novel anticancer compound for the treatment of liver cancer.