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.
- MeSH
- buněčná diferenciace účinky léků MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- endoteliální buňky účinky léků fyziologie MeSH
- estery MeSH
- fixní kombinace léků MeSH
- inhibitory angiogeneze chemická syntéza chemie farmakologie MeSH
- kolagen MeSH
- kyselina gallová analogy a deriváty chemická syntéza farmakologie MeSH
- laminin MeSH
- lidé MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteoglykany MeSH
- silymarin analogy a deriváty chemická syntéza farmakologie MeSH
- stereoizomerie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two selective acylation methods for silybin esterification with long-chain fatty acids were developed, yielding a series of silybin 7-O- and 23-O-acyl-derivatives of varying acyl chain lengths. These compounds were tested for their antioxidant (inhibition of lipid peroxidation and DPPH-scavenging) and anti-influenza virus activities. The acyl chain length is an important prerequisite for both biological activities, as they improved with increasing length of the acyl moiety.
- MeSH
- acylace MeSH
- antioxidancia farmakologie MeSH
- antivirové látky farmakologie MeSH
- buněčné linie MeSH
- esterifikace MeSH
- magnetická rezonanční spektroskopie MeSH
- mastné kyseliny farmakologie MeSH
- molekulární struktura MeSH
- Orthomyxoviridae účinky léků MeSH
- psi MeSH
- silymarin farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.
- MeSH
- anticholesteremika terapeutické užití MeSH
- antiflogistika terapeutické užití MeSH
- antikarcinogenní látky terapeutické užití MeSH
- antioxidancia terapeutické užití MeSH
- apoptóza účinky léků MeSH
- cholagoga a choleretika terapeutické užití MeSH
- financování organizované MeSH
- fytogenní protinádorové látky terapeutické užití MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- kardiotonika terapeutické užití MeSH
- lidé MeSH
- nádory plic prevence a kontrola MeSH
- nádory prostaty farmakoterapie MeSH
- nemoci zvířat farmakoterapie MeSH
- P-glykoprotein účinky léků MeSH
- receptory pro estrogeny účinky léků MeSH
- signální transdukce účinky léků MeSH
- silymarin terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antioxidancia farmakologie chemie MeSH
- jaterní mikrozomy metabolismus MeSH
- játra metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- oxidace-redukce účinky léků MeSH
- scavengery volných radikálů farmakologie chemie MeSH
- silymarin farmakologie chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
