Quantitative structure-activity relationships predicting the antioxidant potency of 17β-estradiol-related polycyclic phenols to inhibit lipid peroxidation

Laszlo Prokai, Nilka M. Rivera-Portalatin, Katalin Prokai-Tatrai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR) studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP) was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration.

Original languageEnglish
Pages (from-to)1443-1454
Number of pages12
JournalInternational journal of molecular sciences
Volume14
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Oxidative stress
Quantitative Structure-Activity Relationship
Phenols
antioxidants
Antioxidants
phenols
Lipids
Lipid Peroxidation
lipids
Estradiol
Oxidative Stress
1-Octanol
Thiobarbituric Acid Reactive Substances
molecular properties
Molecular orbitals
Molecular Structure
logarithms
neurons
markers
Molecular structure

Keywords

  • 17β-estradiol
  • Estrogens
  • Lipid peroxidation
  • Oxidative stress
  • Phenolic antioxidant
  • QSAR
  • TBARS

Cite this

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title = "Quantitative structure-activity relationships predicting the antioxidant potency of 17β-estradiol-related polycyclic phenols to inhibit lipid peroxidation",
abstract = "The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR) studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP) was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration.",
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