title: Cycloaddition of steroidal cyclic nitrones to C=N 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 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.
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary. bobe@chem.u-szeged.hu
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
authors.forename: Judit
authors.initials: J
authors.lastname: Huber
authors.forename: Johanna
authors.initials: J
authors.lastname: Szabó
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.forename: Anasztázia
authors.initials: A
authors.lastname: Hetényi
authors.forename: László
authors.initials: L
authors.lastname: Márk
authors.forename: Gábor
authors.initials: G
authors.lastname: Maász
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Berényi
authors.forename: Ida
authors.initials: I
authors.lastname: Kovács
authors.forename: Renáta
authors.initials: R
authors.lastname: Minorics
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D061565:Cycloaddition Reaction; D004354:Drug Screening Assays, Antitumor; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008872:Microwaves; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D004970:Estrone
keywords: Antiproliferative effect; Dipolar cycloaddition; Estrone; Microwave irradiation; Oxadiazolidinone; Steroid MALDI-TOF