Silychristin

In vitro assessment of human CYP1A1 inhibition potential of Resveratrol and Silychristin[Reference: WebLink]

ongress of the Turkish Toxicology Society. 2015,10.

Flavonoids are phenolic compounds with low molecule weight, which are found most plants in nature. They are so important for human health due to their biological activities such as anti-inflammatory and anti-carcinogenic effects. Cancer protective effects of flavonoids have been attributed to wide variety of mechanisms such as free radical scavenging and modifying Phase I and Phase II enzymes that activate or detoxify carcinogens. Resveratrol and Silychristin are phenolic compounds that may have roles in the reduction of cancer susceptibility. One of the possible mechanism by which resveratrol and Silychristin may exert their anti-carcinogenic effects is through an interaction by certain CYP450s.
METHODS AND RESULTS:
In this respect, the focus of this study is to determine the mechanisms of inhibition of CYP1A1, that is known to be involved in the activation of procarcinogens by resveratrol and Silychristin. Bistronic expression system that coexpress human CYP1A1 and NADPH CYP450 Reductase were used to investigate this effect. Co-expression plasmid was transformed into E. coli DH5alpha. Single colony was selected and grown in overnight culture at 30°C in LB medium. Membrane fractions were prepared and used for enzyme source. Resveratrol inhibited ethoxyresorufin O-deethylation (EROD) activity in human P450 1A1 in a dose-dependent manner with IC50 of 21 μM. Moreover, resveratrol inhibited human P450 1A1 activity in a mixed-type inhibition. In the case of Silychristin, the inhibition of human P450 1A1 by this phenolic compound was stronger than resveratrol. (IC50 15.83 μM for EROD). Similiarly, it showed mixed type inhibition.
CONCLUSIONS:
This study indicated that these phenolics were strong and selective inhibitors of CYP1A1 associated EROD activity and may be considered for use as a strong cancer chemopreventive agent in humans by the preventing malignant transformation and reducing the activations of carcinogens through inhibition of CYP1A1.

Int J Mol Sci. 2015 May 26;16(6):11983-95.

Regioselective alcoholysis of silychristin acetates catalyzed by lipases.[Pubmed: 26016503]

A panel of lipases was screened for the selective acetylation and alcoholysis of Silychristin and Silychristin peracetate, respectively.
METHODS AND RESULTS:
Acetylation at primary alcoholic group (C-22) of Silychristin was accomplished by lipase PS (Pseudomonas cepacia) immobilized on diatomite using vinyl acetate as an acetyl donor, whereas selective deacetylation of 22-O-acetyl Silychristin was accomplished by Novozym 435 in methyl tert-butyl ether/ n-butanol. Both of these reactions occurred without diastereomeric discrimination of Silychristin A and B.
CONCLUSIONS:
Both of these enzymes were found to be capable to regioselective deacetylation of hexaacetyl Silychristin to afford penta-, tetra- and tri-acetyl derivatives, which could be obtained as pure synthons for further selective modifications of the parent molecule.