TY - JOUR
T1 - Quantitative structure-activity relationships predicting the antioxidant potency of 17β-estradiol-related polycyclic phenols to inhibit lipid peroxidation
AU - Prokai, Laszlo
AU - Rivera-Portalatin, Nilka M.
AU - Prokai-Tatrai, Katalin
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - 17β-estradiol
KW - Estrogens
KW - Lipid peroxidation
KW - Oxidative stress
KW - Phenolic antioxidant
KW - QSAR
KW - TBARS
UR - http://www.scopus.com/inward/record.url?scp=84878642468&partnerID=8YFLogxK
U2 - 10.3390/ijms14011443
DO - 10.3390/ijms14011443
M3 - Article
C2 - 23344051
AN - SCOPUS:84878642468
SN - 1661-6596
VL - 14
SP - 1443
EP - 1454
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
ER -