A New Class of Synthetic Flavonolignan-Like Dimers: Still Few Molecules, but with Attractive Properties

Abstract

In recent years, there has been increasing interest in dimeric molecules due to reports of their promising therapeutic value in the treatment of numerous diseases (such as cancer, HIV, Alzheimer's and, malaria). Many reports in the literature have highlighted the ability of these molecules to interact not only with specific biologic receptors but also to induce a biological response that more than doubles the results of the corresponding monomeric counterpart. In this regard, flavonolignan dimers or simply bi-flavonolignans are an emerging class of dimeric compounds that unlike bi-flavonoids, which are very widespread in nature, consist of synthetic dimers of some flavonolignans isolated from the milk thistle Silybum marianum [L. Gaertn. (Asteraceae)]. This mini-review will discuss recent developments in the synthesis, characterization and antioxidant activity of new families of flavonolignan dimers, in light of emerging medicinal chemistry strategies.

Keywords: Silybum marianum; flavonolignans; milk thistle; silibinin; silybin; silymarin.

Figure 1

Classification of naturally occurring flavonolignans.

Figure 2

Main flavonolignans from S. marianum (L. Gaertn. (Asteraceae)).

Figure 3

First bi-flavonolignans from silibinin oxidation and the mechanism of 5′′-5′′ bond formation.

Figure 4

Bi-flavonolignans from dehydro-silybin oxidation.

Figure 5

Bi-flavonolignans from silydianin (8) and silychristine (9) oxidation.

Figure 6

Lipase-catalyzed synthesis of silybin and dehydro-silybin (DHS) dimers (10–11) and synthesis of silibinin dimers with ether spacer (12–13).

Figure 7

Phosphate-Linked Silibinin dimers (PLSd) and building blocks useful for their synthesis.