title: HPLC-based lipophilicity of pyrrolyl-acetic acid ARIs: Relationships with biological activity.
abstract: 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 logP values.
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece.
authors: Marios
authors: M
authors: Chrysanthakopoulos
authors: Ioannis
authors: I
authors: Nicolaou
authors: Vassilis J
authors: VJ
authors: Demopoulos
authors: Anna
authors: A
authors: Tsantili-Kakoulidou
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000085:Acetates / Q000737:chemistry*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D016015:Logistic Models; D000432:Methanol / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000085:Acetates; D004791:Enzyme Inhibitors; D011758:Pyrroles; D014867:Water; D000449:Aldehyde Reductase; D020003:1-Octanol; D000432:Methanol