Genistein is a phytoestrogenic isoflavonoid regarded as a chemo preventive agent. The discovery of pleiotropic genistein activity prompted a search for novel derivatives, expected to exhibit better biochemical or pharmacokinetic characteristics or more selective mechanism of action than the parent compound. The synthesis of glycoconjugates 1 and 2 will be presented and the presence of hex-2-enopyranoside of the molecule as desired structural motif has been demonstrated. We have demonstrated that some of new genistein glycoconjugates (1 and 2) inhibited proliferation of different cancer cell lines at a concentration significantly lower (5–10 times) than the parent compound.
It has been shown that the novel glycoconjugates derivatives of genistein, can inhibit proliferative potential of cancer cells by disruption of microtubule network and mitoticspindle malformation. We report that 1 in contrast to genistein, acts as an aneugen and induces multiplication of centrosomes due to inhibition of microtubule assembly. Flow cytometry and microscopy studies in human cancer cells indicated that glycoconjugates 2 induces cell cycle arrest in the G2/M phase and causes defective mitosis. It was determined also that 1 induces programmed cell death by apoptosis. These results imply that the antimitotic and proapoptotic effects of 1 or 2 may contribute significantly to their potential medicinal applications.
Acknowledgement: Research studies part-financed by the European Union within the European Regional Development Fund (POIG.01.01.02-14-102/09).
References
Gogler-Piglowska A. et al. Cell Biology and Toxicology, 2012, 28, 331-342; Rusin A. et al. Bioorganic & Medicinal Chemistry, 2011, 19, 295-305; Rusin A. et al. Bioorganic & Medicinal Chemistry Letters. 2009, 19, 4939-4943; Polkowski K. et al. Cancer Lett. 2004, 203, 59-69.
