Synthesis and cytotoxic activity of new 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran-5-ones on MCF-7 cells.
A series of eight halogenated 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran-5-ones have been synthesized, characterized and their stereochemistry determined. In a second stage of our work, the reported molecules were tested for their antiproliferative activity on MCF-7 breast carcinoma cells. Pharmacological results were compared with those of diethylstilbestrol (DES), an estrogen, as well as ICI 182,780, a pure antiestrogen. Then, these derivatives were evaluated for their capacity to activate the transcription of a reporter gene and for their affinity for human recombinant estrogen receptors alpha (hER alpha). These results were compared with those of coumestrol, a phytoestrogen structurally close to 2,4-diaryl-4H,5H-pyrano[3,2-c]benzopyran-5-ones, and with RU 58668, a pure antiestrogen. Although these derivatives exhibit a significant antiproliferative activity higher than that of ICI 182,780, neither of them displayed a significant estrogenicity or an affinity for hER alpha. Such results may suggest that their antiproliferative activity is not dependent of an antiestrogenic response.
Jacquot
Y
Y
Service de Chimie Thérapeutique, Faculté de Médecine et de Pharmacie, Laboratoire d'Oncologie et d'Endocrinologie Moléculaire, Besançon, France.
Refouvelet
B
B
Bermont
L
L
Adessi
G L
GL
Leclercq
G
G
Xicluna
A
A
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D003375:Coumestrol / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D045166:Estradiol Congeners / Q000138:chemical synthesis / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D003375:Coumestrol