Homopterocarpanes as bridged triarylethylene analogues: synthesis and antagonistic effects in human MCF-7 breast cancer cells.
A series of new compounds structurally derived from 6a,12a-dihydro-6H,7H-[1]-benzopyran-[4,3-b]-benzopyran (homopterocarpane) was efficiently synthesized by reduction of the corresponding pyrilium salts obtained by treatment of selected flavanones and aldehydes with anhydrous HClO4. Cytotoxic effects on the human breast cancer cell line MCF-7 and antiestrogenic activity (only for compounds which resulted more active than tamoxifen (TAM)) on MCF-7 cells stimulated by 17beta-estradiol were evaluated. In vivo antiestrogenic activity and the relative binding affinity were also assessed. Some of the new compounds (4c, 4h, 4i and 4l) showed a biological activity in the micromolar range, and were more potent than TAM taken as the reference.
Rampa
Angela
A
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. angela.rampa@unibo.it
Bisi
Alessandra
A
Belluti
Federica
F
Gobbi
Silvia
S
Piazzi
Lorna
L
Valenti
Piero
P
Zampiron
Antonella
A
Caputo
Anna
A
Varani
Katia
K
Borea
Pier Andrea
PA
Carrara
Maria
M
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005030:Ethylenes / Q000737:chemistry*; D005260:Female; D044950:Flavanones / Q000737:chemistry; D006801:Humans; D036343:Pterocarpans / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000187:drug effects
D000447:Aldehydes; D000970:Antineoplastic Agents; D005030:Ethylenes; D044950:Flavanones; D036343:Pterocarpans; D011960:Receptors, Estrogen; D004958:Estradiol