Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran, a potent antiestrogenic agent in rats.
OBJECTIVE
To investigate the anti-implantation effect and hormonal profile of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in rats.


METHODS
In vivo assays for anti-implantation activity were performed in pregnant rats. Assays for estrogenicity/antiesrogenicity were performed in immature ovariectomized female rats. In vitro competitive binding of K-1 to human recombinant ERα, transient transfection assay using ERE-luciferase reporter, and alkaline phosphatase (ALP) activity as a measure of estrogenicity and/antiestrogenicity in human endometrial carcinoma cells were performed.


METHODS
Research laboratory.


METHODS
Adult female rats for anti-implantation activity, immature ovariectomized female rats, and immature castrated/intact male rats.


METHODS
None.


METHODS
Number of implantations, uterine growth, luciferase reporter activity, ER binding affinity, and ALP activity.


RESULTS
Compound K-1 given orally for 1-7 days post coitum at the dose of 100 μg/kg body weight prevented pregnancy in 100% of rats. K-1 was a potent antiestrogenic, and at 50 μg/kg, it could inhibit the effect of 1 μg E(2) in immature rats. Compound was devoid of uterotrophic, androgenic, or antigonadotropic activity. A high affinity binding to ERα was displayed by K-1, with a relative binding affinity of 5% of E(2). In human endometrial carcinoma cells, K-1 did not induce ERα-mediated transcriptional activation that is measured as luciferase reporter activity. K-1 antagonized the E-induced transcriptional activation significantly. K-1 also antagonized E-induced ALP activity in human endometrial cells.


CONCLUSIONS
K-1 appeared to exert its antifertility action by virtue of its strong antiestrogenic activity.
Kharkwal
Geetika
G
Division of Endocrinology, Central Drug Research Institute, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, India.
Fatima
Iram
I
Kitchlu
Shakti
S
Singh
Bishambhar
B
Hajela
Kanchan
K
Dwivedi
Anila
A
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000187:drug effects* / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D001578:Benzopyrans; D004965:Estrogen Antagonists; D010880:Piperidines; C099947:2-(4-(2-piperidinoethoxy)phenyl)-3-(4-methoxyphenyl)-2H-benzopyran