Anticancer activity of new cationic arylthiophenes against hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the second most common cancer-related death in the world. No effective curative option exists for the treatment of HCC. The available drugs exhibit severe toxic effects and low therapeutic index.

This work aimed to examine different monocationic arylthiophene derivatives for possible use as chemotherapeutic agents against HCC.

The IC₅₀ values for the compounds were determined. The mechanism of cytotoxicity was further investigated using different methods.

Compound 2j proved to retain the highest cytotoxicity in comparison to as a positive control. The selectivity index of compound 2j revealed the safety to normal cells. Moreover, compound 2j was able to inhibit HepG2 cells´ migration and division. The anticancer effect of compound 2j was found to be partially via cell cycle arrest, activation of the tumour suppressor p53 protein, and induction of apoptosis via both intrinsic and extrinsic pathways. Compound 2j has a potential sensitization activity and significantly reduced the IC₅₀ values for the anticancer drugs doxorubicin, cisplatin, and taxol.

The tested arylthiophenes showed a potent cytotoxicity against HepG2 cells and were safe to normal cells. The most active compound 2j was found to be able to inhibit cell division and migration and also to induce apoptosis. Compound 2j also proved to have a sensitization effect on standard anticancer drugs.