|
|||||
|
|
HPLC-based lipophilicity of pyrrolyl-acetic acid ARIs: Relationships with biological activity |
|
| Authors: | Marios Chrysanthakopoulos Ioannis Nicolaou Vassilis J Demopoulos Anna Tsantili-Kakoulidou |
| Institution: | 1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece;2. Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece |
| 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 log P values. |
| Keywords: | log kw/PB extrapolated retention factors derived using phosphate buffer no addition of n-octanol S/PB the corresponding slope according to Eq (2) log kw0 05/PB extrapolated retention factors derived using phosphate buffer and 0 05% n-octanol in the volume of methanol S0 05/PB the corresponding slope according to Eq (2) log kw0 25/PB extrapolated retention factors derived using phosphate buffer and 0 25% n-octanol in the volume of methanol S0 25/PB the corresponding slope according to Eq (2) log kw/MOPS extrapolated retention factors derived using MOPS no addition of n-octanol S/MOPS the corresponding slope according to Eq (2) log kw0 05/MOPS extrapolated retention factors derived using MOPS and 0 05% n-octanol in the volume of methanol S0 05/MOPS the corresponding slope according to Eq (2) log kw0 25/MOPS extrapolated retention factors derived using MOPS and 0 25% n-octanol in the volume of methanol S0 25/MOPS the corresponding slope according to Eq (2) |
| 本文献已被 ScienceDirect 等数据库收录！ | |