Study of lipophilicity and membrane partition of 4-hydroxycoumarins by HPLC and PCA

Ilijaš, Marina; Malnar, Ivica; Markovic, Vesna; Stepanić, Višnja

doi:10.1016/j.jpba.2012.11.043

Cited by 5 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dataset used in this study was taken from the work reported by Ilijaš, Malnar, Marković, and Stepanić (). This set contains CHI values of 34 derivatives of 4‐hydroxycoumarins, which were measured by HPLC with methanol gradient at pH 7 on a Regis IAM.PC.DD2 (IAM.Phosphatidylcholine.Drug Discovery 2; 150 × 4.6 mm, 12 μm) column.…”

Section: Methodsmentioning

confidence: 99%

Comparative molecular field analysis of chromatographic hydrophobicity indices for some coumarin analogs

Fatemi

Shakoori

Samghani

2016

Biomedical Chromatography

View full text Add to dashboard Cite

The chromatographic hydrophobicity index (CHI) is an HPLC-based parameter that provides reliable guidance in optimization of pharmacological efficiency and adsorption, distribution, metabolism and exertion (ADME) profile of drug candidates. In the present work, classical and three-dimensional quantitative structure-property relationship (QSPR) models were developed for prediction of CHI values of some 4-hydroxycoumarin analogs on immobilized artificial membrane column. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) as 3D-QSPR methods were performed to gain insight into the key structural factors affecting on the chromatographic hydrophobicity of interested chemicals. The calculated parameters of Q , R and standard error were 0.545, 0.996 and 0.773 for CoMFA model and 0.815, 0.986 and 1.44 for CoMSIA model, respectively. The contour maps for steric fields of the CoMFA model illustrate that the hydrophobicity of chemicals will be higher when the positions of R6, R7 and R8 in the 4-hydroxycuomarin ring are substituted by alkyl groups. Moreover, by the analysis of the plots of electrostatic fields, it was concluded that the CHI value greatly increases if one hydrogen on coumarin ring is substituted by the F, Cl, Br, OH or OCH group.

show abstract

Section: Methodsmentioning

confidence: 99%

Comparative molecular field analysis of chromatographic hydrophobicity indices for some coumarin analogs

Fatemi

Shakoori

Samghani

2016

Biomedical Chromatography

View full text Add to dashboard Cite

show abstract

“…These are either calculated by theoretical methods or are experimentally determined (reverse phase-thin layer chromatography) and help us establish the quantitative structure-retention relationship (QSRR). Furthermore, they express the interaction between the cell membranes and the analyzed molecules [ 9 – 13 ].…”

Section: Background and Aimsmentioning

confidence: 99%

Synthesis, lipophilicity and antimicrobial activity evaluation of some new thiazolyl-oxadiazolines

Stoica

Ionuț

Pı̂rnău

et al. 2015

Medicine and Pharmacy Reports

View full text Add to dashboard Cite

Background and aimsSynthesis of new potential antimicrobial agents and evaluation of their lipophilicity.MethodsTen new thiazolyl-oxadiazoline derivatives were synthesized and their structures were validated by 1H-NMR and mass spectrometry. The lipophilicity of the compounds was evaluated using the principal component analysis (PCA) method. The necessary data for applying this method were obtained by reverse-phase thin-layer chromatography (RP-TLC). The antimicrobial activities were tested in vitro against four bacterial strains and one fungal strain.ResultsThe lipophilicity varied with the structure but could not be correlated with the antimicrobial activity, since this was modest.ConclusionsWe have synthesized ten new heterocyclic compounds. After their physical and chemical characterization, we determined their lipophilicity and screened their antimicrobial activity.

show abstract

“…In fact, its use alone in prediction of in vivo drug absorption has been reported to be an oversimplification of a biological complex process leading to inaccuracy in estimation; due to lack of real physiological conditions regulating in vivo membrane permeability (Balimane and Chong, 2008;Hermens, De Bruijn and Brooke, 2013). Several alternative methods such as reversed phase planar chromatography (RPTLC), reversed phase high performance chromatography (RP-HPLC), have been reported for lipophilicity determination of drugs (Ilijas et al, 2013;Hawryl et al 2015;Ciura et al, 2019) but come with flaws of inaccurate measurements due to poor structural similarity of their stationary phase compared to the bio-membrane amphiphilicity. These have made bio-membrane modeling challenging and complex; necessitating use of stationary phase with more complex surface chemistry in reliable simulation of in vivo bio-partitioning process.…”

Section: Introductionmentioning

confidence: 99%

Biomembrane Modelling in Planar Chromatographic Determination of Lipophilicity Using Olive and Castor Oils

Adeyemo¹,

Adeyeye²,

Okeniyi³

2021

njpr

View full text Add to dashboard Cite

BackgroundLipophilicity is a crucial physicochemical parameter that predicts in vivo pharmacokinetics and should be reliably estimated in early stage drug discovery to reduce incidence of attrition. Previous methodologies for its measurement often lead to technically incorrect decisions due to simplistic architecture and poor biomimetic attributes. Significantly, a certain seed oil, used for biomembrane modelling on planar chromatographic platform, was reported to be sufficiently biomimetic and fit for purpose.ObjectivesTo evaluate olive oil (OL) and olive-castor oil (OL-C) equi-mixture as lipids for biomembrane simulation on planar chromatographic platform.Material and MethodRetention behavior of nabumetone, a model compound was used to optimize these potential lipid membranes using a thin film engineered from 5% Liquid paraffin (LP) as benchmark, while halofantrine, nabumetone , α-naphthol and β-naphthol representing varying molecular polarities, were used for validation studies. The validation involved 2-way analysis of variance (ANOVA) associated with variability in Basic lipophilicity parameter (Rmw), and Specific hydrophobic surface area (SHSA) for the optimized surfaces, relative to LP and octadecylsilane (ODS) Further validation entailed correlation of the lipophilicity descriptor i.e. isocratic chromatographic hydrophobicity index (ICHI) on OL, OL-C, ODS and LP with experimental Log P(octanol/water).ResultsOptimized film thicknesses were produced by 5% OL and 1.25% OL-C (p > 0.05). The 2-way ANOVA revealed great variability in performance characteristics of the surfaces (p < 0.0001), and the new surfaces also gave poorer correlation with Log P values (R2= 0.502 and 0.449 respectively).ConclusionThe 1.25 % OL-C demonstrated a higher biomimetic attribute and warrants further validation studies to ascertain biorelevance, of lipophilicity measurement on this platform, in predicting oral drug absorption. Keywords: Lipophilicity, Reversed-phase Thin Layer Chromatography, Retention behaviour, Olive oil, Castor oil

show abstract

Study of lipophilicity and membrane partition of 4-hydroxycoumarins by HPLC and PCA

Cited by 5 publications

References 39 publications

Comparative molecular field analysis of chromatographic hydrophobicity indices for some coumarin analogs

Comparative molecular field analysis of chromatographic hydrophobicity indices for some coumarin analogs

Synthesis, lipophilicity and antimicrobial activity evaluation of some new thiazolyl-oxadiazolines

Biomembrane Modelling in Planar Chromatographic Determination of Lipophilicity Using Olive and Castor Oils

Contact Info

Product

Resources

About