title: Syntheses and antiproliferative effects of D-homo- and D-secoestrones.
abstract: Substituted and/or heterocyclic d-homoestrone derivatives were synthetized via the intramolecular cyclization of a δ-alkenyl-d-secoaldehyde, -d-secoalcohol or -d-secocarboxylic acid of estrone 3-benzyl ether. The d-secoalcohol was modified at three sites in the molecule. The in vitro antiproliferative activities of the new d-homo- and d-secoestrone derivatives were determined on HeLa, MCF-7, A431 and A2780 cells through use of MTT assay. d-Homoalcohols 3 and 5 displayed cell line-selective cytostatic effects against ovarian and cervical cell lines, respectively. Two d-secoestrones (6 and 12c) proved to be effective, with IC50 values comparable with those of the reference agent cisplatin. A selected compound (6) was tested by tubulin polymerization assay and its cancer specificity was additionally determined by using noncancerous human fibroblast cells.
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: 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: Ildikó
authors.initials: I
authors.lastname: Bacsa
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Huber
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: Renáta
authors.initials: R
authors.lastname: Minorics
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Noémi
authors.initials: N
authors.lastname: Bózsity
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: Cereal Research Non-Profit LTD, P.O. Box 391, H-6701 Szeged, Hungary.
authors.forename: Mónika
authors.initials: M
authors.lastname: Varga
authors.affiliation: Virtua Drug Ltd, Csalogány u. 4C, H-1015 Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bikádi
authors.affiliation: Virtua Drug Ltd, Csalogány u. 4C, H-1015 Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Hazai
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 / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004951:Esterification; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008872:Microwaves; D062105:Molecular Docking Simulation; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D004970:Estrone; C012349:D-homoestrone
keywords: Antiproliferative effect; Homoestrone; MTT assay; Secoestrone; Tubulin polymerization