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Iron-chelating effects of flavonoid metabolites - small polyphenolic substances
Vavřichová, Nikol ; Macáková, Kateřina (advisor) ; Karlíčková, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical botanic and ekology Candidate: Nikol Vavřichová Supervisor: Ing. Kateřina Macáková Ph.D. Title of diploma thesis: Iron - chelating effects of flavonoid metabolites - small polyphenolic substances (2015/2016) Iron is a trace element which is necessary for function of an organism. There is no specific excretion mechanism for iron, therefore any deflection causes deficiency or abundance. Iron abundance leads to hemochromatosis. An application of iron chelators is a treatment of choice for hemochromatosis. There are three clinically used chelators for treatment of iron overload: deferoxamine, deferasirox and deferiprone. These drugs are inappropriate for therapy (side effects, dosage form). Therefore there is a place for serching for new types of medicine for treatment of hemochromatosis. Flavonoids are natural substances with positive influence on a human organism. The most investigated effects are antioxidant and chelating activity. As flavonoids are metabolised in a human body, there is an arising question if flavonoid metabolites are also able to chelate iron ions. For this work we chose derivates of benzoic acid: benzoic acid, 3 - hydroxybenzoic acid, 4 - hydroxybenzoic acid, 2,4 - dihydroxybenzoic...
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Enzymatic and Metabolic Transformation of Silybin and its Congeners
Purchartová, Kateřina
Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...
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Enzymatic and Metabolic Transformation of Silybin and its Congeners
Purchartová, Kateřina ; Křen, Vladimír (advisor) ; Macek, Tomáš (referee) ; Vítek, Libor (referee)
Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...
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Iron-chelating effects of flavonoid metabolites - small polyphenolic substances
Vavřichová, Nikol ; Macáková, Kateřina (advisor) ; Karlíčková, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical botanic and ekology Candidate: Nikol Vavřichová Supervisor: Ing. Kateřina Macáková Ph.D. Title of diploma thesis: Iron - chelating effects of flavonoid metabolites - small polyphenolic substances (2015/2016) Iron is a trace element which is necessary for function of an organism. There is no specific excretion mechanism for iron, therefore any deflection causes deficiency or abundance. Iron abundance leads to hemochromatosis. An application of iron chelators is a treatment of choice for hemochromatosis. There are three clinically used chelators for treatment of iron overload: deferoxamine, deferasirox and deferiprone. These drugs are inappropriate for therapy (side effects, dosage form). Therefore there is a place for serching for new types of medicine for treatment of hemochromatosis. Flavonoids are natural substances with positive influence on a human organism. The most investigated effects are antioxidant and chelating activity. As flavonoids are metabolised in a human body, there is an arising question if flavonoid metabolites are also able to chelate iron ions. For this work we chose derivates of benzoic acid: benzoic acid, 3 - hydroxybenzoic acid, 4 - hydroxybenzoic acid, 2,4 - dihydroxybenzoic...
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Enzymatic and Metabolic Transformation of Silybin and its Congeners
Purchartová, Kateřina
Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...
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