Synthesis and cytotoxic activities of E-resveratrol derivatives

The present study was designed to synthesize derivatives of E-resveratrol and evaluate their cytotoxic activity in vitro. Different functional groups were conjugated with the phenolic hydroxyl group of E-resveratrol, and the double bond of E-resveratrol was reduced. The in vitro cytotoxicity of the synthetic derivatives was evaluated against three tumor cell lines (A549, LAC, and HeLa) using the MTT assay. Twenty-six E-resveratrol derivatives were synthesized and their structures were confirmed by 1H NMR, MS, IR, and elemental analyses. Compounds 1–6, 12, 15–21, and 23–26 were reported for the first time. Among them, Compounds 1, 2, 4, 5, and 9–11, showed significant cytotoxicity against tumor cells; especially, Compound 1 showed an IC50 value of 4.38 μmol·L−1 in the A549 cells which was 15-fold more active than E-resveratrol; Compound 9 showed an IC50 value of 1.41 μmol·L−1 in the HeLa cell line which was 90-fold more active than E-resveratrol, and close to adriamycin. The structure-activity relationships were also investigated. Compounds 1, 2 and 9–11 may serve as potential lead compounds for the discovery of new anticancer drugs.

Twenty-six E-resveratrol derivatives were synthesized and their structures were confirmed by 1H NMR, MS, IR, and elemental analyses. Compounds 1–6, 12, 15–21, and 23–26 were reported for the first time. Among them, Compounds, 1, 2, 4, 5, and 9–11, showed significant cytotoxicity against tumor cells; especially, Compound 1 showed an IC50 value of 4.38 μmol·L−1 in the A549 cells which was 15-fold more active than E-resveratrol; Compound 9 showed an IC50 value of 1.41 μmol·L−1 in the HeLa cell line which was 90-fold more active than E-resveratrol, and close to adriamycin. The structure-activity relationships were also investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide