Type II estrogen binding site agonist

Synthesis and biological evaluation of the enantiomers of methyl-para-hydroxyphenyllactate (MeHPLA)

Lester G Pretlow, Roy Williams, Mark Elliott

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A high-affinity ligand for the type II estrogen binding site (EBS) was identified. Methyl para-hydroxyphenyllactate (MeHPLA) was observed to suppress the cellular proliferation of estrogen-sensitive MCF-7 breast cancer cells in vitro and to suppress the growth of rat uteri in vivo. The high affinity of MeHPLA for the type II EBS suggests that this interaction is responsible for the observed suppression of cell growth. In this study, the enantiomers of MeHPLA were synthesized and separated by three methods and evaluated for biological activity. When the methods were compared, it was found that the method using an optically pure amine to form the diastereomers of the enantiomers gave the superior yield. Binding studies for the enantiomers to the type II EBS showed that the S-MeHPLA had a higher affinity for the binding site. However, higher binding affinity did not translate into superior cell growth suppression. Both enantiomers suppressed cell growth equally.

Original languageEnglish (US)
Pages (from-to)674-679
Number of pages6
JournalChirality
Volume15
Issue number8
DOIs
StatePublished - Oct 2 2003

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Enantiomers
Binding sites
Cell growth
Growth
Bioactivity
Uterus
Amines
Rats
Estrogens
Binding Sites
Ligands
Cells
Cell Proliferation
Breast Neoplasms
type II estrogen binding site

Keywords

  • Diastereomers
  • Methylation
  • Racemic
  • Reduction

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

Type II estrogen binding site agonist : Synthesis and biological evaluation of the enantiomers of methyl-para-hydroxyphenyllactate (MeHPLA). / Pretlow, Lester G; Williams, Roy; Elliott, Mark.

In: Chirality, Vol. 15, No. 8, 02.10.2003, p. 674-679.

Research output: Contribution to journalArticle

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