Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents

Abdulrhman Alsayari; Lucas Kopel; Mahmoud Salama Ahmed; Adam Pay; Taylor Carlson; Fathi T. Halaweish

doi:10.1016/j.steroids.2016.11.005

Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents

Abdulrhman Alsayari, Lucas Kopel, Mahmoud Salama Ahmed, Adam Pay, Taylor Carlson, Fathi T. Halaweish

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.

Original language	English (US)
Pages (from-to)	32-40
Number of pages	9
Journal	Steroids
Volume	118
DOIs	https://doi.org/10.1016/j.steroids.2016.11.005
State	Published - 2017
Externally published	Yes

Keywords

Breast cancer
Breast cancer (MCF-7) cell lines
Estrogenic/anti-estrogenic activity
Estrone

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology
Pharmacology
Clinical Biochemistry
Organic Chemistry

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10.1016/j.steroids.2016.11.005

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title = "Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents",

abstract = "Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.",

keywords = "Breast cancer, Breast cancer (MCF-7) cell lines, Estrogenic/anti-estrogenic activity, Estrone",

author = "Abdulrhman Alsayari and Lucas Kopel and Ahmed, {Mahmoud Salama} and Adam Pay and Taylor Carlson and Halaweish, {Fathi T.}",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2017",

doi = "10.1016/j.steroids.2016.11.005",

language = "English (US)",

volume = "118",

pages = "32--40",

journal = "Steroids",

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TY - JOUR

T1 - Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents

AU - Alsayari, Abdulrhman

AU - Kopel, Lucas

AU - Ahmed, Mahmoud Salama

AU - Pay, Adam

AU - Carlson, Taylor

AU - Halaweish, Fathi T.

PY - 2017

Y1 - 2017

N2 - Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.

AB - Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.

KW - Breast cancer

KW - Breast cancer (MCF-7) cell lines

KW - Estrogenic/anti-estrogenic activity

KW - Estrone

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DO - 10.1016/j.steroids.2016.11.005

M3 - Article

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AN - SCOPUS:85006380893

SN - 0039-128X

VL - 118

SP - 32

EP - 40

JO - Steroids

JF - Steroids

ER -

Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents

Abstract

Keywords

ASJC Scopus subject areas

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