title: Inhibition of cancer derived cell lines proliferation by synthesized hydroxylated stilbenes and new ferrocenyl-stilbene analogs. Comparison with resveratrol.
abstract: Further advances in understanding the mechanism of action of resveratrol and its application require new analogs to identify the structural determinants for the cell proliferation inhibition potency. Therefore, we synthesized new trans-resveratrol derivatives by using the Wittig and Heck methods, thus modifying the hydroxylation and methoxylation patterns of the parent molecule. Moreover, we also synthesized new ferrocenylstilbene analogs by using an original protective group in the Wittig procedure. By performing cell proliferation assays we observed that the resveratrol derivatives show inhibition on the human colorectal tumor SW480 cell line. On the other hand, cell viability/cytotoxicity assays showed a weaker effects on the human hepatoblastoma HepG2 cell line. Importantly, the lack of effect on non-tumor cells (IEC18 intestinal epithelium cells) demonstrates the selectivity of these molecules for cancer cells. Here, we show that the numbers and positions of hydroxy and methoxy groups are crucial for the inhibition efficacy. In addition, the presence of at least one phenolic group is essential for the antitumoral activity. Moreover, in the series of ferrocenylstilbene analogs, the presence of a hidden phenolic function allows for a better solubilization in the cellular environment and significantly increases the antitumoral activity.
authors: Université de Bourgogne, 21000 Dijon, France.
authors: Malik
authors: M
authors: Chalal
authors: Université de Bourgogne, 21000 Dijon, France.
authors: Dominique
authors: D
authors: Delmas
authors: Université de Bourgogne, 21000 Dijon, France.
authors: Philippe
authors: P
authors: Meunier
authors: Université de Bourgogne, 21000 Dijon, France. norbert.latruffe@u-bourgogne.fr.
authors: Norbert
authors: N
authors: Latruffe
authors: Université de Bourgogne, 21000 Dijon, France. dominique.vervandier-fasseur@u-bourgogne.fr.
authors: Dominique
authors: D
authors: Vervandier-Fasseur
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D005296:Ferrous Compounds; D013267:Stilbenes; D000077185:Resveratrol