Topoisomerase I/II inhibitor 3 (compound 7) is a potent dual inhibitor of topoisomerase I (Topo I) and II (Topo II) that inhibits the PI3K/Akt/mTOR signaling pathway, subsequently inhibiting cell proliferation, invasion, and migration, and inducing apoptosis. This compound has research value in liver cancer.

Topoisomerase I/II inhibitor 3 (compound 7) (0-100 µM) disrupts DNA topology by intercalation, causing DNA damage [1]. At 0-4 µM over 24 hours, it dose-dependently suppresses the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, including LM9 and HuH7, through MMP-9 inhibition [1]. At 0-14 µM for 48 hours, it induces apoptosis in LM9 and HuH7 cells, along with dose-dependent mitochondrial dysfunction and ROS production [1]. Within 0-7 µM over 48 hours, it decreases Bcl-2 levels while increasing pro-apoptotic proteins like Bax, cytochrome C, cleaved-caspase-3, and cleaved-caspase-9, and obstructs the PI3K/Akt/mTOR pathway [1]. Concentrations from 0-4 µM for 24 hours hinder cell proliferation and colony formation in a concentration-dependent manner, with IC50 values of 2.10 µM for LM9 and 1.93 µM for HuH7. Apoptosis analyses at 0-14 µM over 48 hours confirmed enhanced apoptosis rates concentration-dependently. Western Blot analyses corroborated decreased Bcl-2 expression, increased apoptosis-related proteins, and inhibition of the PI3K/Akt/mTOR signaling pathway [1].

Topoisomerase I/II inhibitor 3, administered intraperitoneally (IP) at doses of 200, 250, and 400 mg/kg to male Kunming mice, resulted in mortality exclusively in the 400 mg/kg cohort, establishing the lethal dose (LD 50) between 250 and 400 mg/kg. The compound, dissolved in 5% DMSO and castor oil, was administered once to four groups of male Kunming mice, each group comprising 8 mice with body weights ranging from 19-22 mg. Observations over a two-week period showed no lethal effects in the 200 mg/kg and 250 mg/kg groups.