Benzo[a]carbazole derivatives. Synthesis, estrogen receptor binding affinities, and mammary tumor inhibiting activity
| Autor: | Erwin von Angerer, J. Prekajac |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Neoplasms
Hormone-Dependent Stereochemistry Carbazoles Estrogen receptor Antineoplastic Agents In Vitro Techniques Cell Line Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Humans Estrogens Non-Steroidal Mammary tumor Carbazole Estrogen receptor binding Uterus Estrogen Antagonists Mammary Neoplasms Experimental Rats Inbred Strains Biological activity Organ Size Affinities In vitro Rats Receptors Estrogen chemistry Biochemistry Molecular Medicine Cattle Female |
| Zdroj: | Journal of Medicinal Chemistry. 29:380-386 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A number of 11-alkylbenzo[a]carbazoles and their 5,6-dihydro derivatives with one or two hydroxy groups in the aromatic rings were synthesized and studied for their binding affinities for the estrogen receptor. Best conditions for the receptor binding are provided by one hydroxy group at C-3 and a second one at position 8 or 9. The binding affinities of the benzo[a]carbazoles are somewhat lower than those of the dihydro derivatives but still high regarding the planar structure of these molecules. The highest relative binding affinity (RBA) values (e.g., 30 for 13b, 13 for 16b, 20 for 25a; estradiol = 100) are close to those of the corresponding 2-phenylindole derivatives. Depending on the positions of the oxygen functions, the benzo[a]carbazoles behaved as strong estrogens (13c, 25a) or impeded estrogens (16c, 28a) in the immature mouse. Derivative 16c inhibited the growth of dimethylbenzanthracene-induced hormone-dependent mammary tumors of the rat at a dose of 6 X 1 mg/kg per week. In vitro, 16b and 28b showed inhibitory activity on estrogen receptor positive MCF-7 breast cancer cells. A mode of action involving the estrogen receptor system is assumed. |
| Databáze: | OpenAIRE |
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