HPLC-based lipophilicity of pyrrolyl-acetic acid ARIs: Relationships with biological activity

Reversed phase HPLC was used to assess the lipophilicity of a series pyrrolyl-acetic acid derivatives with aldose reductase inhibitory activity. The pH conditions were adjusted at 3.0 to investigate the behavior of the neutral species and at pH 7.4, at which the ionized form predominates, using phos...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2010-01, Vol.878 (1), p.61-67
Main Authors: Chrysanthakopoulos, Marios, Nicolaou, Ioannis, Demopoulos, Vassilis J., Tsantili-Kakoulidou, Anna
Format: Article
Language:English
Subjects:
1-Octanol - chemistry
Acetates - chemistry
Aldehyde Reductase - antagonists & inhibitors
Aldehyde Reductase - metabolism
Aldose reductase inhibitory activity
Analysis
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Enzyme Inhibitors - chemistry
Fundamental and applied biological sciences. Psychology
General pharmacology
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Kinetics
Lipophilicity
Logistic Models
Medical sciences
Methanol - chemistry
n-Octanol as mobile phase additive
Pharmacology. Drug treatments
Pyrroles - chemistry
Pyrrolyl-acetic acid derivatives
RP-HPLC
Water - chemistry
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Summary:Reversed phase HPLC was used to assess the lipophilicity of a series pyrrolyl-acetic acid derivatives with aldose reductase inhibitory activity. The pH conditions were adjusted at 3.0 to investigate the behavior of the neutral species and at pH 7.4, at which the ionized form predominates, using phosphate and MOPS buffer. Retention was monitored in absence and in presence of different amounts of n-octanol in the mobile phase in order to explore the chromatographic conditions which best reproduce the octanol–water partition or distribution coefficients. The effect of n-octanol in retention was systematically studied and its role in lipophilicity assessment was evaluated. Nevertheless rather moderate regression equations were obtained, which deviated significantly from the ideal 1:1 correlation. No significant effect of buffer was observed. The appropriateness of retention factors to be used in correlation with aldose reductase inhibitory activity was further evaluated and compared to the efficiency of the corresponding octanol–water log P values.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2009.11.020