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Silychristin: Skeletal Alterations and Biological Activities

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† Institute of Microbiology, Laboratory of Biotransformation, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Prague, Czech Republic
‡ Stolařská 601/4, CZ 747 14 Ludgeřovice, Czech Republic
§ Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo náměstí 2, CZ 166 10 Prague, Czech Republic
⊥ CZ-OPENSCREEN: National Infrastructure for Chemical Biology, Institute of Molecular Genetics, Czech Academy of Sciences, Vídeňská 1083, CZ 142 20 Praha 4, Czech Republic
*Tel: +420241062360. Fax: +420244471 286. E-mail: [email protected]
Cite this: J. Nat. Prod. 2016, 79, 12, 3086–3092
Publication Date (Web):November 22, 2016
https://doi.org/10.1021/acs.jnatprod.6b00750
Copyright © 2016 The American Chemical Society and American Society of Pharmacognosy
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    Abstract

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    Silychristin is the second most abundant flavonolignan (after silybin) present in the fruits of Silybum marianum. A group of compounds containing silychristin (3) and its derivatives such as 2,3-dehydrosilychristin (4), 2,3-dehydroanhydrosilychristin (5), anhydrosilychristin (6), silyhermin (7), and isosilychristin (8) were studied. Physicochemical data of these compounds acquired at high resolution were compared. The absolute configuration of silyhermin (7) was proposed to be identical to silychristin A (3a) in ring D (10R,11S). The preparation of 2,3-dehydrosilychristin (4) was optimized. The Folin–Ciocalteau reduction and DPPH and ABTS radical scavenging assays revealed silychristin and its analogues to be powerful antioxidants, which were found to be more potent than silybin and 2,3-dehydrosilybin. Compounds 4–6 exhibited inhibition of microsomal lipoperoxidation (IC50 4–6 μM). Moreover, compounds 4–8 were found to be almost noncytotoxic for 10 human cell lines of different histogenetic origins. On the basis of these results, compounds 3–6 are likely responsible for most of the antioxidant properties of silymarin attributed traditionally to silybin (silibinin).

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.6b00750.

    • 1H and 13C NMR data, MS, ECD, and UV spectra of all new compounds, and HPLC chromatograms of all new final products, synthesis of 4, its optimization, and cell profiling with human cell lines (PDF)

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