Chemometrics approach based on chromatographic behavior, in silico characterization and molecular docking study of steroid analogs with biomedical importance

Karadžić, Milica; Jevrić, Lidija R.; Mandić, Anamarija; Markov, Siniša; Podunavac‐Kuzmanović, Sanja O.; Kоvаčеvić, Strаhinjа; Nikolić, Andrea R.; Oklješa, Aleksandar M.; Sakač, Marija N.; Penov-Gaši, Katarina M.

doi:10.1016/j.ejps.2017.05.004

Cited by 13 publications

(5 citation statements)

References 56 publications

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“…One of the key properties responsible for skin permeability of solutes is lipophilicity. Some earlier chromatographic studies of lipophilicity of steroids and steroid analogues [ 45 , 46 ] were based on the linear extrapolation approach. Chromatographic parameters for a single-solvent mobile phase were obtained by using a series of chromatographic experiments with mobile phases containing different concentrations φ of a modifier.…”

Section: Resultsmentioning

confidence: 99%

RP-18 TLC Chromatographic and Computational Study of Skin Permeability of Steroids

2021

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The skin permeability of steroids, as investigated in this study, is important because some of these compounds are, or could, be used in preparations applied topically. Several models of skin permeability, involving thin layer chromatographic and calculated descriptors, were generated and validated using Kp reference values obtained in silico and then tested on a group of solutes whose experimental Kp values could be found (log Kpexp). The study established that the most applicable log Kp model is based on RP-18 thin layer chromatographic data (RM) and the calculated descriptors VM (molar volume) and PSA (polar surface area). Two less efficient, yet simple, equations based on PSA or VM combined with HD (H-donor count) can be used with caution for rapid, rough estimations of compounds’ skin permeability prior to their chemical synthesis.

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Section: Resultsmentioning

confidence: 99%

RP-18 TLC Chromatographic and Computational Study of Skin Permeability of Steroids

2021

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“…A number of papers underline the correlation between lipophilicity and ADME properties (Karadžić et al, ; Milošević, Stojanović, Penov‐Gaši, Perišić‐Janjić, & Kaliszan, ; Trifunović, Borčić, Vukmirović, Goločorbin Kon, & Mikov, ). In these papers chromatographic lipophilicity parameters are used to predict some ADME properties.…”

Section: Resultsmentioning

confidence: 99%

QSAR characterization of new synthesized hydantoins with antiproliferative activity

Tot

Lazić

Božić

et al. 2019

Biomedical Chromatography

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Hydantois have been identified as constituents of a number of pharmacologically active molecules. In the present study, we have examined in vitro antiproliferative activity against human colon cancer cell lines HCT-116 of three series of 3-(4substituted benzyl)-hydantoins with various substituent attached in position 5 of the hydantoin ring. Since the investigated compounds have recently been synthesized and show antiproliferative activity, a good understanding of the properties of the potential drug responsible for their pharmacokinetics is an important goal for their further development. One of the important properties is lipophilicity. Lipophilicity has been assessed by reversed-phase liquid chromatography (high-performance thin-layer chromatography and high-pressure liquid chromatography) by means of direct and indirect (using calibration curve) methods. Chromatographic lipophilicity indices in addition to calculated logP values were compared by hierarchical cluster analysis. The linear solvation energy relationship approach was used to understand and compare the types and relative strength of the molecular interactions that occur in the chromatographic as well as in the n-octanol-water partitioning systems. Finally, correlation between in silico pharmacokinetic predictors and antiproliferative activity was examined. Preliminary quantitative structure-activity relationship modeling indicates that pharmacokinetic predictors capture only one-quarter of all chemical features that are important for antiproliferative activity itself. Among selected descriptors are chromatographic lipophilicity indices.

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“…Another possibility is the use of an interpolation method with the calibration set of compounds with known log P and a single TLC run. Also, the retention data can be used in different chemometric treatments (principal component analysis [PCA] and parallel factor analysis) to extract the lipophilicity values (Šegan et al, 2022; Kovačević et al, 2020; Karadžić et al, 2017; Komsta et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of lipophilicity and drug‐likeness of donepezil‐like compounds using reversed‐phase thin‐layer chromatography

Šegan,

Krunić,

Andrić

et al. 2024

Biomedical Chromatography

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Fourteen donepezil‐like acetylcholinesterase (AChE) inhibitors from our library were analyzed using reversed‐phase thin‐layer chromatography to assess their lipophilicity and blood–brain barrier permeability. Compounds possessed N‐benzylpiperidine and N,N‐diarylpiperazine moieties connected via a short carboxamide or amine linker. Retention parameters RM0, b, and C0 were considered as the measures of lipophilicity. Besides, logD of the investigated compounds was determined chromatographically using standard compounds with known logPow and logD values at pH 11. Experimentally obtained lipophilicity parameters correlated well with in silico generated results, and the effect of the nature of the linker between two pharmacophores and substituents on the arylpiperazine part of the molecule was observed. As a result of drug‐likeness analysis, both Lipinski's rule of five and Veber's rule parameters were determined, suggesting that examined compounds could be potential candidates for further drug development. Principal component analysis was performed to obtain an insight into a grouping of compounds based on calculated structural descriptors, experimentally obtained values of lipophilicity, and AChE inhibitory activity.

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Chemometrics approach based on chromatographic behavior, in silico characterization and molecular docking study of steroid analogs with biomedical importance

Cited by 13 publications

References 56 publications

RP-18 TLC Chromatographic and Computational Study of Skin Permeability of Steroids

RP-18 TLC Chromatographic and Computational Study of Skin Permeability of Steroids

QSAR characterization of new synthesized hydantoins with antiproliferative activity

Evaluation of lipophilicity and drug‐likeness of donepezil‐like compounds using reversed‐phase thin‐layer chromatography

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