Assessment of lipophilicity of newly synthesized celecoxib analogues using reversed-phase HPLC

Abstract

Abstract Background Lipophilicity is a physicochemical property of an essential importance in medicinal chemistry; therefore, fast and reliable measurement of lipophilicity will affect greatly the drug discovery process. Results A series of N-benzenesulfonamide-1H-pyrazoles, oximes and hydrazones as celecoxib analogues was investigated with regard to their retention behavior using reversed-phase high performance liquid chromatography (RP-HPLC). The mobile phases employed for this study consist of a mixture of water and methanol in different proportions. In addition, the stationary phase utilized for this separation was C18 silanized silica gel and using 200 nm as a detection wavelength. The retention behavior of the investigated compounds was determined based on practical determination of log k at different concentrations of methanol (as an organic modifier) in the mobile phase ranging from 60 to 80%. It was observed that the retention of these compounds (expressed as log k) decreased in a linear manner with increasing the concentration of methanol. High correlation coefficients (more than 0.90 in most cases) were obtained for the relationship between the volume fraction of the organic solvent and the retention values represented as log k w. A comparative evaluation was carried out between chromatographically-obtained lipophilicity parameters (represented as lipophilicity chromatographic index log k w or isocratic chromatographic hydrophobicity index, $$\varphi$$ φ 0) and the computationally calculated log P values (miLogP, ALOGP, ACD/Labs and ALOGPs). Conclusion It was found that a good correlation exists between the experimental and computed log P values. In the future, these results can give a deep insight about the anti-inflammatory and analgesic activity of the newly synthesized compounds.

Keywords

• Lipophilicity estimation
• Celecoxib analogues
• HPLC
• Lipophilicity chromatographic index
• log k w