3-Fluoro-evodiamine glucose (Compound 8) is an evodiamine-glucose conjugate. It enhances the expression of glucose transporter 1 (GLUT1) and inhibits topoisomerase I/II activity. Additionally, 3-Fluoro-evodiamine glucose induces apoptosis and causes cell cycle arrest at the G2/M phase. This compound demonstrates anti-tumor activity both in vivo and in vitro, with no significant toxicity observed.

3-Fluoro-evodiamine glucose (0-0.5 μM, 12 h) demonstrates antiproliferative activity and cytotoxicity in cancer cell lines U87MG, A549, and HCT116 by inducing reactive oxygen species (ROS) accumulation and DNA damage, with an IC₅₀ range of 0.064–0.113 μM. Additionally, 3-Fluoro-evodiamine glucose (0-0.05 μM, 24 h) inhibits HCT116 cell migration and invasion in a dose-dependent manner.

Administered at a dose of 10 mg/kg via intraperitoneal injection, 3-Fluoro-evodiamine glucose exhibits favorable pharmacokinetic properties in mice, with a half-life of 2.41 hours, a maximum plasma concentration (C max) of 4627 h·ng/mL, and an area under the curve (AUC 0-t) of 4008 h·ng/mL. The mean residence time is 0.802 hours. Additionally, at doses of 10-20 mg/kg administered twice daily for 21 days via intraperitoneal injection, this compound demonstrates antitumor activity in HCT116 xenograft nude mice, achieving a tumor growth inhibition rate (TGI) of 72%-82% without significant toxicity.