Resveratrol Derivatives with a Urea Backbone Exert Anticancer Effects against Liver Cancer via Apoptosis Induction and Metastasis Inhibition
- J Agric Food Chem. 2025 Dec 10;73(49):31429-31443. doi: 10.1021/acs.jafc.5c14000.
- 1. College of Food Science and Nutrition Engineering; Jilin Province Brewing Technology Science and Technology Innovation Center, Jilin Agricultural Science and Technology College, 77th Han Lin Road, Jilin City 132101, P.R. China.
- 2. Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Anti-Tumor Molecular Target Technology Innovation Center; College of Life Science, Hebei Normal University, Shijiazhuang 050024, P.R. China.
Hepatocellular carcinoma remains a fatal disease with a high metastasis risk. Matrix Metalloproteinases (MMPs) are key mediators of metastasis and are potential therapeutic targets. Using a natural product derivatization strategy, we designed novel Anticancer agents based on resveratrol─a dietary polyphenol found in grapes and Other food sources with known MMP-suppressive effects. Although the resveratrol derivative amino-Res (5) showed promising in vitro activity, its poor metabolic stability limited its in vivo efficacy. To address this, we synthesized 14 urea-containing derivatives of amino-Res. Among them, compound 6k exhibited improved metabolic stability and potent Anticancer activity both in vitro and in vivo. Mechanism studies revealed that 6k arrests the cell cycle in the G2/M phase, induces intrinsic Apoptosis, and inhibits migration and invasion through MMP suppression. This work demonstrates the value of derivatizing dietary natural products for developing novel Anticancer agents.