Genistein, one of the major soy isoflavones is a promising agent for cancer chemoprevention. There are many experimental evidence showing that the inhibition of human cancer cell growth by genistein is mediated via the modulation of genes related to the control of the cell cycle and apoptosis.[1] Several glycoconjugates of genistein appeared more active than parent compound in preliminary screening for inhibition of cancer cell proliferation. The most potent compound was Ram-3, in which genistein is linked with a 2,3-unsaturated sugar moiety through an alkyl chain containing three carbon atoms.[2]

In the present study we report the synthesis of new glycoconjugates of genistein. We also describe the results of preliminary in vitro screening of antiproliferative and proapoptotic activity of several representatives of these glycoconjugates in cancer cells. Inhibition of proliferation was assessed in MTT assay, cell cycle was studied with flow cytometer. Mitotic and apoptotic indices and cell senescence were determined by microscopical observation.

Our results indicate the role of the sugar moiety is essential for activity  of compounds. It is necessary to maintain the half-chair conformation of sugar moiety as an important structural factor. In particular the 2,3-unsaturated sugars and 2,3-anhydro derivatives (oxiranes) are the objects of interest. Moreover, polyfunctional sugar moieties offer ample opportunities for almost continuous changes in shape, electron density and polarity. Change of the protecting groups led us to derivatives with wide range of lipophilicity, which significantly differ in anti-cancer activity.

Research studies part-financed by the European Regional Development Fund (POIG. 01.01.02-14-102/09).

[1] S. Banerjee, Y. Li, Z. Wang, F.H. Sarkar, Cancer Letters, 2008, 269, 226-242
[2] A. Rusin, J. Zawisza-Puchałka, K. Kujawska, A. Gogler-Pigłowska, J. Wietrzyk, M. Świtalska, M. Głowala-Kosińska, A. Gruca, W. Szeja, Z. Krawczyk, G. Grynkiewicz, Bioorg. Med. Chem. Lett., 2011, 19, 259-305

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