Design, synthesis and biological evaluation of novel urolithin derivatives targeting liver cancer cells

We designed and synthesised 22 new urolithin derivatives (UDs) based on methyl-urolithin A (mUA) to identify anti-cancer drugs with high efficacy and low toxicity and evaluated their anti-cancer activities <i>in vitro</i>. Cytotoxicity tests were performed on three cell lines (DU145, T24, and HepG2) and a human normal cell line (HK-2). The half-inhibitory concentration (IC₅₀) of derivative UD-4c to hepatoma HepG2 cells (IC₅₀ = 4.66 ± 0.12 μM) was significantly lower than that of sorafenib (IC₅₀ =7.76 ± 0.12 μM), and exhibited less toxicity to HK-2 cells. Preliminary studies on the mechanism revealed that the derivative UD-4c could significantly inhibit the HepG2 cell growth and colony formation, block the HepG2 cell cycle in the G2/M phase, and induce apoptosis of HepG2 cells dose-dependently. The derivative UD-4c can be used as a potential lead compound to further develop new drugs for hepatocellular carcinoma treatment based on the evaluation of anti-cancer activity.