New dinorneolignans from Cedrela odorata and other analogues with potential antiangiogenic properties

Lignans and neolignans are known dietary polyphenols found in plants. Numerous studies reveal that these compounds can be promising chemotherapeutic/chemopreventive agents. Their anticancer activity can occur through the induction of apoptosis, inhibition of cell proliferation, and the hindering of metastasis and angiogenesis [1]. In the course of our screening project on antiangiogenic specialized metabolites, a pool of lignan and neolignan derivatives isolated from different plant sources were investigated. Plant materials were extracted with solvents of increasing polarity, including n-hexane, CHCl3, CHCl3-MeOH 9:1, and MeOH. The compounds were isolated using different chromatographic techniques such as flash chromatography by Biotage Isolera, Sephadex LH-20, and RP-HPLC and their structures were identified using 1D and 2D NMR (COSY, HSQC, HMBC, ROESY), ECD, and HRESIMS data. Two new dinorneolignans were obtained from Cedrela odorata L. (Meliaceae) stem bark and characterized as 9-acetyltoonin C and treo-guaiacylglycerol-beta-methyl vanillate ether. Other known lignans and neolignans were obtained from two conifers belonging to Podocarpus genus (Podocarpaceae) [2, 3] and from Salvia macilenta Boiss (Lamiaceae). All compounds were investigated for their antiangiogenic activity using zebrafish (Danio rerio) in vivo model. Among the isolates, treo-guaiacylglycerol-beta-methyl vanillate ether and erythro-4,7,9,9’-tetrahydroxy-3,3’-dimethoxy-8-O-4’-oxyneolignan induced the best antiangiogenic response at 10 µM on the release of endogenous alkaline phosphatase by endothelial cells as a marker of embryo vessel growth. In conclusion, this study suggests the potential role of isolated lignan derivatives as new therapeutic agents able to modulate angiogenesis.