[Gamma-hydroxybutyric acid, a metabolite of UFT, shows anti-angiogenic activities and antitumor effect].

We investigated the antitumor vasculogenesis and antitumor activity of gamma-hydroxybutyric acid (GHB), a metabolite of UFT. In a mouse dorsal air sac (DAS) assay, UFT demonstrated a wide spectrum of anti-tumor vasculogenesis except for AZ-521 tumor. Although the expression of vascular endothelial growth factor (VEGF) was detected in almost all tumor cell lines used in the DAS assays, expression of basic fibroblast growth factor (bFGF) was only detected in the AZ-521 tumor. GHB inhibited the chemotactic migration and morphological changes of human umbilical vein endothelial cells (HUVECs) induced by VEGF at IC50 values of 2.8 and 0.31 microM respectively. In addition to these in vitro assays, GHB blocked tumor growth of MC-5, a human breast cancer, in a xenograft model at inhibition rate of 37%. Moreover, GHB showed an additive effect in combination with 5-FU in this model. These results indicate that the anti-tumor vasculogenesis activity of GHB is involved in part in the antitumor effect of UFT.

Synthesis and cytostatic activity of 4,7-dihydroxythioaurone derivatives. Effect of B ring substitution on the activity.

Biological activity of thioaurones was not tested so far and the group constitute completely unexplored source of new molecules of pharmacological interest. We report synthesis and evaluation of cytotoxic activity of thioaurone derivatives bearing p-hydroquinone system in ring A. Their activity was found to depend strongly on substitution pattern, so eventually both the activity and pharmacokinetic parameters of the molecules could be tailored by further structural modifications.