Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran, a potent antiestrogenic agent in rats

Geetika Kharkwal, Iram Fatima, Shakti Kitchlu, Bishambhar Singh, Kanchan Hajela, Anila Dwivedi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 E2 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 E2. 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.

Original languageEnglish (US)
Pages (from-to)1322-1327
Number of pages6
JournalFertility and Sterility
Volume95
Issue number4
DOIs
StatePublished - Mar 15 2011

Fingerprint

Luciferases
Alkaline Phosphatase
Endometrial Neoplasms
Transcriptional Activation
Competitive Binding
2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran
Human Activities
Transfection
Body Weight
Outcome Assessment (Health Care)
Pregnancy
Growth
Research

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran, a potent antiestrogenic agent in rats. / Kharkwal, Geetika; Fatima, Iram; Kitchlu, Shakti; Singh, Bishambhar; Hajela, Kanchan; Dwivedi, Anila.

In: Fertility and Sterility, Vol. 95, No. 4, 15.03.2011, p. 1322-1327.

Research output: Contribution to journalArticle

Kharkwal, Geetika ; Fatima, Iram ; Kitchlu, Shakti ; Singh, Bishambhar ; Hajela, Kanchan ; Dwivedi, Anila. / Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran, a potent antiestrogenic agent in rats. In: Fertility and Sterility. 2011 ; Vol. 95, No. 4. pp. 1322-1327.
@article{9e04e58d055a4097a0e32ae6a44f31fa,
title = "Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran, a potent antiestrogenic agent in rats",
abstract = "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 E2 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 E2. 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.",
author = "Geetika Kharkwal and Iram Fatima and Shakti Kitchlu and Bishambhar Singh and Kanchan Hajela and Anila Dwivedi",
year = "2011",
month = "3",
day = "15",
doi = "10.1016/j.fertnstert.2010.06.066",
language = "English (US)",
volume = "95",
pages = "1322--1327",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran, a potent antiestrogenic agent in rats

AU - Kharkwal, Geetika

AU - Fatima, Iram

AU - Kitchlu, Shakti

AU - Singh, Bishambhar

AU - Hajela, Kanchan

AU - Dwivedi, Anila

PY - 2011/3/15

Y1 - 2011/3/15

N2 - 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 E2 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 E2. 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.

AB - 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 E2 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 E2. 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.

UR - http://www.scopus.com/inward/record.url?scp=79952452810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952452810&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2010.06.066

DO - 10.1016/j.fertnstert.2010.06.066

M3 - Article

VL - 95

SP - 1322

EP - 1327

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 4

ER -