title: Synthesis and antiangiogenic activity of new silybin galloyl esters.
abstract: The synthesis of various silybin monogalloyl esters was developed, and their antiangiogenic activities were evaluated in a variety of in vitro tests with human umbilical vein endothelial cells (HUVECs). A structure-activity relationship (SAR) study found the regioselectivity of the silybin galloylation to be highly significant. Silybin (as an equimolar mixture of two diastereomers A and B) exhibited quite poor antiangiogenic activities, whereas its B stereoisomer is more active than silybin A. The galloylation of phenolic OH groups of natural silybin (a mixture of both isomers) leads to increases in their antiangiogenic activities, which is more apparent with the 7-OH than the 20-OH. In contrast, gallates at aliphatic OH groups either had a comparable activity to the parent compound or are even worse than silybin, which was observed in the case of 3-O-galloylsilybin. The most effective compound from this series (7-O-galloylsilybin) has also been prepared from stereochemically pure silybins A and B to evaluate the effect of stereochemistry on the activity. As with silybin itself, the B isomer of 7-O-galloylsilybin was more active than the A isomer.
authors.affiliation: Centre of Biotransformation and Biocatalysis, Institute of Microbiology Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague 4, CZ 142 20, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Gažák
authors.forename: Kateřina
authors.initials: K
authors.lastname: Valentová
authors.forename: Kateřina
authors.initials: K
authors.lastname: Fuksová
authors.forename: Petr
authors.initials: P
authors.lastname: Marhol
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Medina
authors.forename: Ivana
authors.initials: I
authors.lastname: Oborná
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004952:Esters; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin; D011509:Proteoglycans; D000077385:Silybin; D012838:Silymarin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C568966:7-O-galloylsilybin; D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D004952:Esters; D007797:Laminin; D011509:Proteoglycans; D012838:Silymarin; C059485:matrigel; D000077385:Silybin; D005707:Gallic Acid; D003094:Collagen