2-Phenylbenzo[b]furans: relationship between structure, estrogen receptor affinity and cytostatic activity against mammary tumor cells.
A number of 2-(4-hydroxyphenyl)benzo[b]furans with a hydroxy group in position 5 or 6 and a short alkyl group at C-3 were synthesized from appropriate 1,2-diarylethanones and studied for their estrogen receptor affinity. The relative binding affinities in the 5-hydroxy series were higher than those of 6-hydroxy derivatives by a factor of 10. The trifluoroethyl and the propyl derivatives displayed the best relative binding affinity values (33 (15a) and 20 (12a); 17 beta-estradiol = 100). All benzofurans with high receptor affinity were tested for specific cytostatic activity using hormone-sensitive human MCF-7 mammary tumor cells and hormone-independent MDA-MB 231 cells. 5-Hydroxy derivatives with an ethyl (11a) or a propyl (12a) group completely inhibited the growth of MCF-7 cells at a concentration of 5 microM (tamoxifen: 70% inhibition). Since the cytostatic activity in MDA-MB 231 cells was much lower, an anti-tumor effect mainly mediated by the estrogen receptor has to be assumed. In the mouse uterine weight test these compounds gave rise to a partial estrogen antagonism which may account for the inhibitory effect in estrogen-sensitive tumor cells.
Erber
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S
Institut für Pharmazie, Universität Regensburg, Germany.
Ringshandl
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von Angerer
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D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001572:Benzofurans; D011960:Receptors, Estrogen; D004958:Estradiol