C‐Glycosidic Genistein Conjugates and Their Antiproliferative Activity

Abstract

This paper presents our attempt to investigate scopes and the limitations of olefin cross-metathesis (CM) reaction in the synthesis of complex C-glycosides of genistein and evaluation of their antiproliferative activities. Novel genistein glycoconjugates were synthesized with the utility of CM reaction initiated by first and second generation of Grubbs catalysts. The relative reactivity of utilized olefins, based on categories proposed by Grubbs, was estimated.In vitroexperiments in cancer cell lines showed that the selected derivatives (3aand3f) exhibited higher antiproliferative potential than the parent compound, genistein, and were able to block the cell cycle in the G2/M phase. The observed mechanism of action of C-glycosidic derivatives was similar to the activity of their O-glycosidic counterparts. These compounds were stable in culture medium. The obtained results show that our approach to genistein modification with application of cross-metathesis reaction allowed to obtain stable glycoconjugates with improved anticancer potential, compared to the parent isoflavone.

Detection of flavone C-glycosides in the extracts from the bark of Prunus avium L. and Prunus cerasus L.

“…antioxidant potential, whereas O-glycosylation reduces flavonoid bioactivity and (iii) although the structure of aglycone is responsible for the bioactivity, the bioactivity of flavonoid C-glycosides may be different from that of the aglycones. [1][2][3][4][5][6] Recently, a systematic increase in the number of papers devoted to the flavonoid C-glycosides has been noted, in particular those devoted to the one specific flavonoid C-glycoside known to show interesting biological activities. For example vitexin or isovitexin show a number pharmacological properties, however, the most promising seems to be their anticancer activity.…”

Synthetic Genistein Glycosides Inhibiting EGFR Phosphorylation Enhance the Effect of Radiation in HCT 116 Colon Cancer Cells

“…The relatively simple structure of the genistein molecule and the many possibilities of its derivatization offer ample space for obtaining derivatives with improved activity or affecting new molecular targets [24]. In the previous work, we described glycoconjugates of genistein inhibiting cancer cell proliferation more efficiently than genistein [25,26,27,28,29]. The aim of this work was to evaluate EGFR tyrosine kinase inhibition by selected genistein derivatives and to explore the biological effects of these compounds used in combination with ionizing radiation.…”

Phytochemicals for the Management of Melanoma

“…Several studies have shown that genistein glycoconjugates (Fig. 10D) exhibit anti-proliferative potential [313, 317, 318] and even induce cell cycle arrest [319, 320]. Interestingly, some of these analogs also inhibited microtubule assembly [318, 319, 321].…”