Cycloaddition of steroidal cyclic nitrones to CN dipolarophiles: Stereoselective synthesis and antiproliferative effects of oxadiazolidinones in the estrone series

Abstract Cyclic nitrones of estrone 3-methyl or 3-benzyl ether were reacted with phenyl isocyanate or nonsubstituted phenyl isocyanates as reactive C N 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 C 70 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.