The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of p-glycoprotein

https://doi.org/10.1016/S0960-894X(99)00636-8 Get rights and content

Abstract

A new series of potential flavonoidic modulators of P-glycoprotein activity has been prepared. The flavanolignan silybin was first oxidised to dehydrosilybin and then C-alkylated with either prenyl or geranyl bromide. The resulting isoprenoid dehydrosilybins were shown to display high in vitro affinities for direct binding to P-glycoprotein, which ranged them among the best flavonoids ever tested.

References (16)

  • V Lecureur et al.

    FEBS Lett.

    (1994)
  • M.M Gottesman et al.

    Annu. Rev. Biochem.

    (1993)
  • P Gros et al.

    Int. Rev. Cytol.

    (1993)
  • J.M Pérez-Victoria et al.

    Biochemistry

    (1999)
  • C.F Higgins

    Annu. Rev. Cell. Biol.

    (1992)
  • A.B Shapiro et al.

    Eur. J. Biochem.

    (1999)
  • G Conseil et al.

    Proc. Natl. Acad. Sci. USA

    (1998)
  • G Dayan et al.

    Biochemistry

    (1997)
There are more references available in the full text version of this article.

Cited by (85)

  • Synthesis of poinsettifolin A

    2014, Tetrahedron
    Citation Excerpt :

    The direct prenylation of electron-rich phenolic compounds has been reported, although it is known to be a challenge to obtain selective prenylation at only one position in a compound like 2. The use of prenyl halides in the presence of a base, e.g. DBU,14 tetramethylammonium hydroxide,15,16 potassium hydroxide17,18 or sodium hydride,19,20 failed as C-prenylated products were obtained together with O-prenylated as well as degradation products of 3 (2 is not stable in basic conditions). Next, Lewis acid catalysed condensation of 2-methyl-3-buten-2-ol was attempted.

  • Design, economical synthesis and antiplasmodial evaluation of vanillin derived allylated chalcones and their marked synergism with artemisinin against chloroquine resistant strains of Plasmodium falciparum

    2014, European Journal of Medicinal Chemistry
    Citation Excerpt :

    A close scrutiny of natural antimalarial chalcones has revealed that a vast majority of these possess substituted allylated aromatic rings (prenyl or geranyl group) as important elements of their pharmacophores. The importance of prenyl or allyl group for enhancing the bioactivities of flavonoids and chalcones is well documented in literature [22,30–33]. Furthermore, the prenyl moiety contributes to the lipophilicity of the molecule, an important requirement for antimalarial activity [34].

  • Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

    2022, Journal of Evidence-Based Integrative Medicine
View all citing articles on Scopus
View full text