title: Synthesis and in vitro antiproliferative evaluation of d-secooxime derivatives of 13β- and 13α-estrone.
abstract: d-Secooximes were synthesized from the d-secoaldehydes in the 13β- and 13α-estrone series. The oximes were modified at three sites in the molecule: the oxime function was transformed into an oxime ether, oxime ester or nitrile group, the propenyl side-chain was saturated and the 3-benzyl ether was removed in order to obtain a phenolic hydroxy function. Triazoles were formed via Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC) from 3-(prop-2-yniloxy)-d-secooximes and benzyl azides. All the products were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7, A2780 and A431). Some of them exhibited activities with submicromolar IC50 values, better than that of the reference agent cisplatin. The structural modifications led to significant differences in the cytostatic properties. Flow cytometry indicated that one of the most potent agents resulted in a cell cycle blockade.
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary. Electronic address: bobe@chem.u-szeged.hu.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fiser
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Johanna
authors.initials: J
authors.lastname: Szabó
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bodnár
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Ida
authors.initials: I
authors.lastname: Kovács
authors.affiliation: Department of Biochemistry, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D049109:Cell Proliferation / Q000187:drug effects*; D061565:Cycloaddition Reaction; D004354:Drug Screening Assays, Antitumor; D004970:Estrone / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D014230:Triazoles; D004970:Estrone
keywords: 13α-Estrone; Antitumor activity; Cell cycle blockade; Oxime; Secoestrone