skip to menu

Preparation of silybin (2,3-dehydrosilybin) derivatives with the inhibitory action on transport proteins (MDR – proteins, P-glycoprotein)

One of the plausible explanations for synergistic effects of silybin and anti-cancer drugs is inhibition of efflux function of dominant multidrug resistance (MDR) transporter P-glycoprotein [].

We have identified effective and relatively non-cytotoxic inhibitors of Pgp derived from 2,3-dehydrosilybin (2) (Fig. 1). Some of them were more effective inhibitors at lower concentrations than a standard Pgp efflux inhibitor cyclosporine A. Another group of 2,3-dehydrosilybin derivatives had also better inhibitory effects on Pgp efflux but a cytotoxicity was comparable with parent 2,3-dehydrosilybin. Structural requirements for improving inhibitory activity and reducing toxicity of 2,3-dehydrosilybin were established. Effect of E-ring substitution as well as an influence of the substituent size at the 7-OH position of A-ring on Pgp-inhibitory activity was evaluated for the first time in this study [].

Figure 1. Structures of the most active inhibitors of Pgp prepared from 2,3-dehydrosilybin (2)

Structures of the most active inhibitors of Pgp prepared from 2,3-dehydrosilybin


Financial support

This work was supported by the Czech Ministry of Education (Research concepts No. MSM 6198959216, MSM 0021620835 and AV0Z50200510) and KONTAKT project No. 7–2006–16.


  1. Maitrejean, M.; Comte, G.; Barron, D.; El Kirat, K.; Gwenaelle, C.; Di Pietro, A. Bioorg. Med. Chem. Lett. 2000, 10, 157
  2. Džubák P, Hajdúch M, Gažák R, Svobodová A, Psotová J, Walterová D, Sedmera P, Křen V. New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity. Bioorg Med Chem 2006;14:3793–3810

Institute of Microbiology - Czech Academy of Sciences