title: Effects of 2,3-Dehydrosilybin and Its Galloyl Ester and Methyl Ether Derivatives on Human Umbilical Vein Endothelial Cells.
abstract: The effects in vitro of 2,3-dehydrosilybin and several galloyl esters and methyl ethers on the viability, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) were evaluated. The monogalloyl esters were synthesized by a chemoselective esterification method or by Steglich esterification of suitably protected 2,3-dehydrosilybin (1) with protected gallic acid. 2,3-Dehydrosilybin (1) displayed more potent cytotoxic, antiproliferative, and antimigratory activities (IC50 12.0, 5.4, and 12.2 μM, respectively) than silybin. The methylated derivatives were less active, with the least potent being 3,7-di-O-methyl-2,3-dehydrosilybin (6). On the other hand, galloylation at C-7 OH and C-23 OH markedly increased the cytotoxicity and the effects on the proliferation and migration of HUVECs. The most active derivative was 7-O-galloyl-2,3-dehydrosilybin (13; IC50 value of 3.4, 1.6, and 4.7 μM in the cytotoxicity, inhibition of proliferation, and antimigratory assays, respectively). Overall, this preliminary structure-activity relationship study demonstrated the importance of a 2,3-double bond, a C-7 OH group, and a galloyl moiety in enhancing the activity of flavonolignans toward HUVECs.
authors.forename: Daniel
authors.initials: D
authors.lastname: Karas
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Gažák
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Valentová
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chambers
authors.forename: Veronika
authors.initials: V
authors.lastname: Pivodová
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Biedermann
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Křenková
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, Palacký University and University Hospital , I.P. Pavlova 6, CZ-775 20 Olomouc, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Oborná
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences , Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Cvačka
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
authors.affiliation: Institute of Microbiology, Czech Academy of Sciences , Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Křen
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry; D005707:Gallic Acid / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008738:Methyl Ethers / Q000494:pharmacology; D015394:Molecular Structure; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016166:Free Radical Scavengers; D008738:Methyl Ethers; D012838:Silymarin; C515097:dehydrosilybin; D000077385:Silybin; D005707:Gallic Acid