Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).
ID: CHEMBL4402507
Journal: Bioorg Med Chem
Title: Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).
Authors: Kim JY, Kim JY, Jenis J, Li ZP, Ban YJ, Baiseitova A, Park KH.
Abstract: Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1-7) inhibited both monophenolase (IC<sub>50</sub> = 1.7-7.6 µM) and diphenolase (IC<sub>50</sub> = 12.1-44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8-10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of E<sub>met</sub>·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with K<sub>SV</sub> values of 0.06-0.27 × 10<sup>4</sup> L·mol<sup>-1</sup>, which are well correlated with IC<sub>50</sub>s. In kinetic study, all flavonolignan (1-7) were mixed type I (K<sub>I</sub> < K<sub>IS</sub>) inhibitors, whereas their mother skeletons (8-10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.
CiteXplore: 30871862
Patent ID: ---
| ChEMBL ID | Target Similarity | Compound Similarity | Reference | Title | PubMed ID | DOI |
|---|---|---|---|---|---|---|
| CHEMBL2331134 | 1 | 0.03 | Bioorg Med Chem (2013) 21:2156-2162 | Design and synthesis of 3,5-diaryl-4,5-dihydro-1H-pyrazoles as new tyrosinase inhibitors. | 23391365 | 10.1016/j.bmc.2012.12.054 |
| CHEMBL3098052 | 1 | 0.06 | Bioorg Med Chem Lett (2014) 24:122-125 | Chemical synthesis and tyrosinase inhibitory activity of rhododendrol glycosides. | 24332496 | 10.1016/j.bmcl.2013.11.063 |
| CHEMBL3102744 | 1 | 0.06 | Bioorg Med Chem (2014) 22:1115-1120 | Inhibition of tyrosinase activity by polyphenol compounds from Flemingia philippinensis roots. | 24412339 | 10.1016/j.bmc.2013.12.047 |
| CHEMBL3286294 | 1 | 0 | Bioorg Med Chem Lett (2014) 24:2150-2154 | Buthionine sulfoximine diverts the melanogenesis pathway toward the production of more soluble and degradable pigments. | 24703231 | 10.1016/j.bmcl.2014.03.031 |
| CHEMBL3351773 | 1 | 0.06 | Bioorg Med Chem (2014) 22:3994-4000 | Effect of p-aminophenols on tyrosinase activity. | 24972725 | 10.1016/j.bmc.2014.05.073 |
Protein Target Summary
Total
1
Fungi
Assay Summary
Total
17
B - Binding
Bioactivity Summary
Total
129
Ki
IC50
Kis
Inhibition
KA
KSV
Activity
TIME
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