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

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-1 H -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 C 18 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, 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. Electronic supplementary material The online version of this article (10.1186/s13065-019-0607-6) contains supplementary material, which is available to authorized users.

Simultaneous effect of different chromatographic conditions on the chromatographic retention of pentapeptide derivatives (HGRFG and NPNPT)

“…Generally, a wider range of methanol concentrations correlates with more accurate coefficients. A previous study reported the linear relationship of and φ at 60%–80% methanol ( Elmansi et al, 2019 ). However, in our study, the pentapeptides analyzed generally had short carbon chains with high polarity and showed low retention in RP-HPLC.…”

Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer

“…In vitro release profile of free CXB revealed that 25.9% of the free drug was released after 5 h, then it started to precipitate in PBS at pH 7.4 due to its hydrophobicity and low dissolution rate in water 60 , 61 . While formulated CXB revealed a sustained release profile as only 5.9% was released after 5 h. This small amount of released drug might be due to adsorption of some drug molecules on the outer surface of the NPs 31 .…”

High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors

“…It also represents concentration of the organic modifier in the mobile phase resulting in the retention time (t R ) that is double the dead time (t 0 ). Therefore, it can be accurately estimated which is considered a distinguishable advantage over extrapolating of logk values to pure water mobile phase [38]. This parameter was also proved to be more suitable for the estimation of lipophilicity of sets of structurally unrelated compounds [39,40].…”

“…This parameter was also proved to be more suitable for the estimation of lipophilicity of sets of structurally unrelated compounds [39,40]. Although introduced almost thirty years ago, this parameter is still used for the estimation of lipophilicity of various classes of bioactive compounds [38,41].…”