Study On The Design, Synthesis And Antitumor Activity Of 2 - Methoxy Estradiol Skeletal Analogues

As a novel tumor angiogenesis inhibitor,2-Methoxyestradiol (2ME2) has progressed into clinical trials phase Ⅱ-Ⅲ for treatment of various solid cancers. Considering the special structure of2-Methoxyestradiol, we designed and synthesized non-steroid analogs with similar structure to2-ME-the analogues of3’-methoxy-E-diethylstilbestrol and2-phenylindoles. In addition, a number of sulfamates of target compounds were synthesized and evaluated as steroid sulfatase inhibitors.All of the target compounds and some of intermediates have been screened against the cell lines of HUVEC, RL95-2, SKOV-3, MCF-7and T-47D. The biological screening data indicated:the analogues of3’-methoxy-E-diethylstilbestrol showed potential anti-tumor activities and the mechanism of action may be similar to2-Methoxyestradiol; the introduction of ethyl side chain into the3-position of2-phenylindoles increased the inhibitory effect. Compound131and137exhibited considerable activities with IC50values between10μM and45μM.