Enzymatic esterification of flavonoids with unsaturated fatty acids: Effect of the novel esters on vascular endothelial growth factor release from K562 cells

Rutin and naringin were enzymatically acylated with different free mono- and poly-unsaturated fatty acids (mufa and pufa) using the immobilized lipase B from Candida antarctica (Novozym 435 ®) in acetone at 50 °C. Conversion yields for naringin and rutin were 85 and 70%, respectively, using oleic acid as acyl donor. The conversion of rutin was slightly affected by the nature of the free unsaturated fatty acid used. Compared to the direct esterification of rutin with linoleic acid, its transesterification with ethyl linoleate exhibited a lower conversion (50%). The enzymatic acylation of rutin and naringin is regioselective since only monoesters were identified. Additionally, the ability of both flavonoids and their esters to modulate the secretion of vascular endothelial growth factor (VEGF), a major regulator of tumor-induced angiogenesis, was examined in K562 lymphoblastoma cell line. Compared to the effect of parental molecules, rutin and individual fatty acids, the synthesized esters were more efficient in reducing the release of VEGF from K562 cells indicating that they might possess improved anti-angiogenic and anti-tumor properties.