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 journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)32-40
Number of pages9
JournalSteroids
Volume118
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Estrogen Receptors
Estrogens
Molecular Docking Simulation
Competitive Binding
Estrone
Cell proliferation
Cytotoxicity
Computer Simulation
Assays
Cell Proliferation

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

Cite this

Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents. / Alsayari, Abdulrhman; Kopel, Lucas; Ahmed, Mahmoud Salama; Pay, Adam; Carlson, Taylor; Halaweish, Fathi T.

In: Steroids, Vol. 118, 01.01.2017, p. 32-40.

Research output: Contribution to journalArticle

Alsayari, Abdulrhman ; Kopel, Lucas ; Ahmed, Mahmoud Salama ; Pay, Adam ; Carlson, Taylor ; Halaweish, Fathi T. / Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents. In: Steroids. 2017 ; Vol. 118. pp. 32-40.
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