Modifications of benzylphenoxy ethanamine antiestrogen molecules: influence affinity for antiestrogen binding site (AEBS) and cell cytotoxicity
| Autor: | Fabienne Mésange, Marc Poirot, Blandine Kedjouar, Francis Bayard, Frédéric Delarue, Jean-Charles Faye |
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| Přispěvatelé: | Poirot, Marc, Endocrinologie et communication cellulaire, Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
MESH: Rats
Cell Survival Stereochemistry Estrogen receptor MESH: Binding Competitive Antineoplastic Agents MESH: Estrogen Antagonists MESH: Research Support Non-U.S. Gov't Binding Competitive Biochemistry Cell Line HeLa Animals Humans MESH: Animals Binding site Cytotoxicity Pharmacology MESH: Humans Binding Sites biology Ligand Chemistry Cell growth Estrogen Antagonists MESH: Comparative Study [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Antiestrogen biology.organism_classification In vitro MESH: Cell Line Rats MESH: Hela Cells [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences Tamoxifen MESH: Binding Sites MESH: Cell Survival Receptors Estrogen MESH: Antineoplastic Agents MESH: Receptors Estrogen MESH: Tamoxifen HeLa Cells |
| Zdroj: | Biochemical Pharmacology Biochemical Pharmacology, Elsevier, 1999, 57, pp.657-61 |
| ISSN: | 0006-2952 1873-2968 |
| Popis: | The antiestrogen binding site (AEBS) is a membranous protein complex that has been shown to be intimately linked with the antiproliferative and antiretroviral effects of certain antiestrogenic compounds such as tamoxifen (Tx). Various specific ligands of AEBS derived from benzylphenoxy ethanamine and a new benzoyl structure were synthesized either by modification of the aminoether side chain or by halogen substitution at the meta-, ortho-, and para position on the benzoyl group. Using the MCF-7 cellular strain and its RTx6 variant (a clone selected for its antigrowth resistance to tamoxifen), it was shown that under high drug concentrations the cytotoxicity of the ligands was directly correlated with their affinity for AEBS. In agreement with previous observations made on triphenylethylenic ligands, modification of the basic ethanamine side chain modulated the ligand affinities. Chloride in meta increased ligand efficacy, whereas chloride substitution in ortho and para decreased it. Effects on AEBS-positive MCF-7 cells were drug concentration- and time-dependent, whereas they were unspecific on the AEBS-negative RTx6 cell line. These cytotoxic effects were confirmed in the absence of estrogen receptor on human AEBS-positive uterine cervix cell carcinoma HeLa cells, but were non-specific on rat fibroblastic AEBS-negative (low concentration) NRK cells. The cytotoxicities of these ligands are related to their affinities for AEBS. |
| Databáze: | OpenAIRE |
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