Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Steroids. 2013 Oct;78(10):1021-8. doi: 10.1016/j.steroids.2013.06.009. Epub 2013 Jul 4.
Cyclic nitrones of estrone 3-methyl or 3-benzyl ether were reacted with phenyl isocyanate or nonsubstituted phenyl isocyanates as reactive CN dipolarophiles, yielding condensed homosteroidal oxadiazolidinones. These dipolar cycloadditions were carried out under conventional heating or microwave irradiation. The chemo- and stereoselectivities of the reactions and the effects of the aromatic substituents on the reaction rates and yields were investigated and compared. The structures of the new products were determined by NMR (one- and two-dimensional) and MALDI-MS techniques, with C70 fullerenes as matrix in the latter case. The antiproliferative properties of the synthetized compounds were determined on a panel of human adherent cell lines (HeLa, MCF7, A2780 and A431) by means of MTT assays. Some of them exhibited activities comparable to that of the reference agent cisplatin. Flow cytometry indicated that one of the most potent agents (11a) resulted in a cell cycle blockade.
雌酮 3-甲基或 3-苄醚的环状亚硝酮与苯异氰酸酯或未取代的苯异氰酸酯反应，作为反应性 CN 双烯亲偶体，生成缩合的同甾体噁二唑烷酮。这些偶极环加成反应在常规加热或微波辐射下进行。研究并比较了反应的化学选择性和立体选择性，以及芳基取代基对反应速率和产率的影响。通过 NMR（一维和二维）和 MALDI-MS 技术确定了新产物的结构，在后一种情况下，使用 C70 富勒烯作为基质。通过 MTT 测定法，在一组人贴壁细胞系（HeLa、MCF7、A2780 和 A431）上测定了合成化合物的抗增殖特性。其中一些表现出与参比药物顺铂相当的活性。流式细胞术表明，最有效的药物之一（11a）导致细胞周期阻滞。
