Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines.

Genistein, the principal soy isoflavone, is a molecule of great interest as an innovative chemotherapeutic agent or as a lead-compound in anticancer drug design. To enhance intrinsic activity of genistein and to explore its pharmacophoric potential, its glycosidic derivatives were synthesized. On the basis of structural features and calculated lipophilicity coefficient (ClogP) the derivatives were classified as hydrophilic (i.e. those containing free sugar moiety) or lipophilic (i.e. those with alkylated or acylated sugar hydroxyls). The in vitro cytostatic and cytotoxic studies showed hydrophilic glycosides to be practically inactive against human cancer cell lines when compared to the free aglycone. On the contrary, lipophilic glycosides were significantly more active than the parent isoflavone although the correlation between ClogP and the activity was not clear. On the basis of GI50 and LC50 values two of the most active glycosides were found to be several times more potent in their cytostatic and cytotoxic effect than genistein. Additionally all lipophilic glycosides were revealed to exhibit different mode of action in comparison to genistein. It may suggest that these compounds do not undergo rapid biodegradation, either in culture media or inside cells, and exert their biological effects primarily as intact molecules.

Determination of new derivatives of genistein in culture media by liquid chromatography.

Methods for determination of genistein and its four new analogues in culture media have been developed to support studies on their potential anticancer activities. The investigated compounds were extracted from the media using liquid-liquid extraction with appropriate solvent. After evaporation of organic solvents each of the dry extracts was reconstituted in appropriate mobile phase. Reversed-phase HPLC was applied to quantitative determining of tested compounds. The methods are specific, sensitive and technically simple. They were used to evaluate concentration level of investigated compounds in experiments with human promyelocytic leukemia cells (HL-60 cell line).