.7 - Hydroxy -3 - (4 - Hydroxyphenyl) -6 - Methoxy-4h-chromene -4 - Ketone And Its Derivatives, And Biological Activity

2-Methoxyestradiol (2-ME,1) is a novel angiogenic inhibitor, which is being investigated in the pre-clinical and clinical trials for treatment of various solid cancers, especially breast cancer, prostate cancer and multiple myeloma. Recently most studies on the structural modifications of 2-ME were focused on the steroid rings and the groups such as 3-hydroxyl, 17-hydroxyl or 2-methoxyl. However, there are rare researches on replacing the steroidal scaffold of 2-ME with some non-steroidal backbones reported.7-hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one (4) is one important component of soy isoflavones and shows fascinating bioactivities on preventing cardiovascular disease and regulating estrogen-level. The fact that 4 has the heterocyclic ring similar to estra-ring and same groups as 2-ME at corresponding positions promoted us to synthesize and explore the anti-angiogenic activity of this compound. Consequentially, 4 exhibits potential inhibitor activity on the Human Umbilical Vein Endothelial Cells model with EC₅₀ as 47.37μM (2-ME as refrence,EC50 = 8.59μM).Furthermore, we plan to establish carbon-carbon, carbon-nitrogen, or carbon-sulphur bond respectively on the 4-position of 4 and introduce various groups into the position based on the chemical property of carbonyl. In this study, the physical and chemical properties of this kind of compounds were revealed gradually and there are rigorous requirements for the nucleophiles about their steric hindrance and surface charge since the specific characteristic of 4-position carbonyl group. All of the target compounds and some intermediates have been examined by using the HUVEC, A549( human lung cancer cell), DU-145(human prostate cancer cell) model. Among the 27 new compounds, 6 compounds display anti-angiogenic activity (the IC₅₀ value are less than 50μM on HUVEC), 8 compounds are effective on inhibiting the growth of A549 cells and DU-145 cells (the GI₅₀ value are less than 20 μg/mL.