OBJECTIVE: To investigate the anti-implantation effect and hormonal profile of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in rats. DESIGN: 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. SETTING: Research laboratory. ANIMAL(S): Adult female rats for anti-implantation activity, immature ovariectomized female rats, and immature castrated/intact male rats. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of implantations, uterine growth, luciferase reporter activity, ER binding affinity, and ALP activity. RESULT(S): 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. CONCLUSION(S): K-1 appeared to exert its antifertility action by virtue of its strong antiestrogenic activity.
OBJECTIVE: To investigate the anti-implantation effect and hormonal profile of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in rats. DESIGN: 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 humanendometrial carcinoma cells were performed. SETTING: Research laboratory. ANIMAL(S): Adult female rats for anti-implantation activity, immature ovariectomized female rats, and immature castrated/intact male rats. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of implantations, uterine growth, luciferase reporter activity, ER binding affinity, and ALP activity. RESULT(S): 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 humanendometrial 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. CONCLUSION(S): K-1 appeared to exert its antifertility action by virtue of its strong antiestrogenic activity.
Authors: V Chandra; I Fatima; M Manohar; P Popli; V K Sirohi; M K Hussain; K Hajela; P Sankhwar; A Dwivedi Journal: Cell Death Dis Date: 2014-08-21 Impact factor: 8.469