Ενζυμική σύνθεση ακυλιωμένων παραγώγων φυσικών αντιοξειδωτικών σε μη συμβατικά συστήματα. Αξιολόγηση της βιολογικής και αντιοξειδωτικής τους δράσης

• Main Authors: Mellou, Foteini, Μέλλου, Φωτεινή
• Format: Doctoral or Postdoctoral Thesis
• Language: Greek
• Published: National Technical University of Athens (NTUA) 2006
• Subjects: Βιοκατάλυση; Αντιοξειδωτικά; Λιπάση; Εστεροποίηση; Φλαβονοειδή; Αγγειογένεση; Πολυακόρεστα λιπαρά οξέα; Ενδοθηλιακός αυξητικός παράγοντας; Biocatalysis; Antioxidants; Lipase; Esterification; Flavonoids; Angiogenesis; Polyunsaturated fatty acids; Vascular endothelial growth factor (VEGF); Επιστήμες Μηχανικού και Τεχνολογία; Επιστήμη Χημικού Μηχανικού; Engineering and Technology; Chemical Engineering; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10442/hedi/16201; https://doi.org/10.12681/eadd/16201

The present PhD thesis focuses on the enzymatic synthesis of acylated derivatives of natural antioxidants with fatty acids in non-conventional media. The purification of the synthesized products and the evaluation of their biological properties were also studied. A single-step acylation of the flavonoids rutin and naringin, with mono and polyunsaturated fatty acids was performed using an immobilized Candida antarctica lipase in non-toxic organic solvents. The influence of the reaction parameters on the performance of the biocatalytic process was pointed out using the acylation of rutin with oleic acid as a model reaction. The aim of this study was to find the optimal reaction parameters for the acylation of rutin and naringin to prepare esters in high yield. The effect of the quantity of lipase, the water content, the temperature, the molar ratio of flavonoid to acyl donor, as well as the nature of the acyl donor and the nature of the solvent were investigated. Under the optimal conditions found, the esters of rutin and naringin with oleic acid, linoleic acid, ethyl linoleate acid and γ-linolenic acid were obtained The enzymatic acylation of rutin and naringin is regioselective since only monoesters were identified. The purification of the flavonoid esters produced by large scale enzymatic production was studied. The chemical structure of the flavonoid esters was determined by spectroscopic techniques. The antioxidant activities of the novel compounds were evaluated for their capacity to scavenge DPPH radicals. 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. Moreover, the ...