title: Synthesis and biological evaluation of novel tamoxifen analogues.
abstract: A collection of compounds, structurally related to the anticancer drug tamoxifen, used in breast cancer therapy, were designed and synthesized as potential anticancer agents. McMurry coupling reaction was used as the key synthetic step in the preparation of these analogues and the structural assignment of E, Z isomers was determined on the basis of 2D-NOESY experiments. The compounds were evaluated for their antiproliferative activity on breast cancer (MCF-7), cervix adenocarcinoma (HeLa) and biphasic mesothelioma (MSTO-211H) human tumor cell lines. The estrogen like properties of the novel compounds were compared with those of the untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay and compared to 17β-estradiol (E2). Finally, with the aim to correlate the antiproliferative activity with an intracellular target(s), the effect on relaxation activity of DNA topoisomerases I and II was assayed.
authors.affiliation: Chemistry Laboratory, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.forename: Nikolas
authors.initials: N
authors.lastname: Fokialakis
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
authors.forename: Aída Nelly
authors.initials: AN
authors.lastname: García-Argáez
authors.forename: Ornella Maria
authors.initials: OM
authors.lastname: Gia
authors.forename: Ingemar
authors.initials: I
authors.lastname: Pongratz
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Serkos A
authors.initials: SA
authors.lastname: Haroutounian
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D013629:Tamoxifen