Synthesis and Antiangiogenic Activity of New Silybin Galloyl Esters

0369330 - MBÚ 2012 RIV US eng J - Journal Article
Gažák, Radek - Valentová, K. - Fuksová, Kateřina - Marhol, Petr - Kuzma, Marek - Medina, M. A. - Oborná, I. - Ulrichová, J. - Křen, Vladimír
Synthesis and Antiangiogenic Activity of New Silybin Galloyl Esters.
Journal of Medicinal Chemistry. Roč. 54, č. 20 (2011), s. 7397-7407. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR GAP207/10/0288; GA ČR(CZ) GAP301/11/0767; GA MŠMT OC08049
Institutional research plan: CEZ:AV0Z50200510
Keywords : Silybin * gallates * HUVEC
Subject RIV: CC - Organic Chemistry
Impact factor: 5.248, year: 2011

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 isomer is more active than silybin A. 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 7-O-galloylsilybin has also been prepared from pure silybins A and B. B isomer was more active than A isomer
Permanent Link: http://hdl.handle.net/11104/0203423