Discovery of a novel 10-hydroxy-12-methyl-substituted evodiamine derivative with anti-hepatocellular carcinoma activity through multi-pathway modulation involving suppression of PKA/AKT signaling cascades and moderate Topo I inhibition.
Z4 more effectively inhibited proliferation and migration/invasion of BEL-7404 and HuH-7 cells than sorafenib, while inducing cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and apoptosis, and provides a promising lead compound Z4 for anti-HCC drug discovery.