Reversed-phase Thin-layer Chromatography Research Articles

Aniline Derivatives Containing 1-Substituted 1,2,3-Triazole System as Potential Drug Candidates: Pharmacokinetic Profile Prediction, Lipophilicity Analysis Using Experimental and In Silico Studies

Background: The triazole ring is an attractive structural unit in medicinal chemistry, and chemical compounds containing this type of system in their structure exhibit a wide spectrum of biological activity. They are used in the development of new pharmaceuticals. One of the basic parameters considered in the initial phase of designing potential drugs is lipophilicity, which affects the bioavailability and pharmacokinetics of drugs. Methods: The study aimed to assess the lipophilicity of fifteen new triazole derivatives of aniline using reversed phase thin layer chromatography (RP-TLC) and free web servers. Based on in silico methods, the drug similarity and pharmacokinetic profile (ADMET) of synthesized molecules were assessed. Results: A relationship was observed between the structure of the title compound, including the position of substitution in the aniline ring, and the experimental values of lipophilicity parameters (logPTLC). Most of the algorithms used to determine theoretical logP values showed less sensitivity to structural differences of the tested molecules. All obtained derivatives satisfy the drug similarity rules formulated by Lipinski, Ghose and Veber. Moreover, in silico analysis of the ADME profile showed favorable values of parameters related to absorption.

Synthesis, Structure, and In Vitro Biological Evaluation of Semi-Synthetic Derivatives of Betulin

Betulin and α-lipoic acid are naturally occurring substances with different biological properties. Combining two phytochemical units into a conjugate is a frequently used method to obtain new compounds with better pharmacokinetic parameters. This research concerned the preparation of lipoate derivatives of betulin using the Steglich method. Experimental lipophilicity values were determined for target compounds 6–10 by reversed-phase thin-layer chromatography. In silico methods were used to calculate the physicochemical parameters and lipophilicity of new derivatives and to determine the probable directions of biological activity. α-Lipoic acid, betulin, and lipoate derivatives 6–10 were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, HCT116, MiaPaca-2, and Hs294T cancer cells. 3-(5-(1,2-Dithiolan-3-yl)pentanoyl))betulin 10 showed moderate anticancer activity against MV4-11, PC-3, and HCT116, with IC50 values in the range of 39.8–76.7 µM. The introduction of a dithiolate substituent at the C3 position in 28-acetylbetulin gave compound 9 the highest activity (IC50 = 37.9 µM), in the ratio of biphenotypic B myelomonocytic leukemia cells (MV4-11). All lipoate derivatives were inactive towards normal cells.

Analysis of Lipophilicity and Pharmacokinetic Parameters of Dipyridothiazine Dimers with Anticancer Potency.

Lipophilicity is an essential parameter of a compound that determines the solubility and pharmacokinetic properties that determine the transport of the drug to the molecular target. Dimers of dipyridothiazines are diazaphenothiazine derivatives exhibiting diverse anticancer potential in vitro, which is related to their affinity for histone deacetylase. In this study, the lipophilicity of 16 isomeric dipyridothiazine dimers was investigated theoretically and experimentally by reversed-phase thin-layer chromatography (RP-TLC) in an acetone-TRIS buffer (pH = 7.4). The relative lipophilicity parameter RM0 and specific hydrophobic surface area b were significantly intercorrelated, showing congeneric classes of dimers. The parameter RM0 was transformed into parameter logPTLC by use of the calibration curve. Molecular descriptors, ADMET parameters and probable molecular targets were determined in silico for analysis of the pharmacokinetic profile of the tested compounds showing anticancer activity. The analyzed compounds were tested in the context of Lipinski's rule of five, Ghose's rule and Veber's rule, confirming their bioavailability.

Assessment of the Lipophilicity of Indole Derivatives of Betulin and Their Toxicity in a Zebrafish Model.

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logPTLC) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logPTLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds.

Evaluation of greenness, blueness, and whiteness with analytical quality by design assisted instrumental reversed-phase thin-layer chromatography‒densitometric approach to estimate monosodium glutamate in commercial food samples using green-ultrasound-assisted extraction technique

Evaluation of greenness, blueness, and whiteness with analytical quality by design assisted instrumental reversed-phase thin-layer chromatography‒densitometric approach to estimate monosodium glutamate in commercial food samples using green-ultrasound-assisted extraction technique

Chromatographic descriptors in QSAR examination of the N, N-disubstituted chloroacetamides’ bioactivity

The main goal of this study was the assessment of the N, N-disubstituted-2-chloroacetamides’ biological profile by chromatographic and in silico approach. Preliminary, their drug-like as well as lead-like properties and the bioactivity scores were analyzed. By applying reversed phase thin-layer chromatography as the simulator of compound’s distribution across biological membranes, the assumed bioactivity descriptors of the studied chloroacetamides were obtained. The compliance between obtained chromatographic parameters (R M,0 m) and relevant software lipophilicity/pharmacokinetic/ecotoxicity predictors of studied derivatives were examined by linear regression and additionally supported by more detailed relations established by multivariate methods. Also, it was confirmed that the studied bioactivity properties of the given chloroacetamides are conditioned by the type of the present hydrocarbon substituents (number, arrangement and binding of C atoms).

Synthesis and cytotoxicity of copper(II) semicarbazone complexes with lipophilic counter-anions

A series of (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) perfluoroalkyl carboxylato copper(II) complexes, [CF3(CF2)nCO2(LH)Cu] (LH2 = 2,4-dihydroxybenzaldehyde dibenzyl semicarbazone; n = 0, 2, 4, 6; 1–4), and (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) pyridine copper(II) perfluoroalkyl carboxylates, [(LH)(py)Cu]+[CF3(CF2)nCO2]− (5–8) were synthesized. The lipophilicity of these compounds was determined by reverse-phase thin layer chromatography and correlated with their cytotoxicity towards MOLT-4 human leukaemia cells. Cytotoxicity is more strongly correlated with lipophilicity for the non-ionic compounds (1–4) than for the ionic compounds (5–8). Compounds 5–8 (IC50 2.8–3.8 μM) are generally more cytotoxic than compounds 1–4 (IC50 3.6–8.4 μM). They also exhibit slightly higher cytotoxicity than the parent anticancer compound [(LH)(py)Cu]+[NO3]− (IC50 4.15 μM), suggesting that it is possible to enhance the cytotoxicity of [(LH)(py)Cu]+[NO3]− by replacing nitrate with anions of higher lipophilicity. Attempts to synthesize the non-fluorinated analogue [(LH)(py)Cu]+[CH3CO2]− resulted in the formation of the deprotonated complex [L(py)Cu], whose structure was confirmed by X-ray crystallography. The structural parameters indicate that the deprotonation site is the hydrazonic nitrogen of the semicarbazone ligand.

Reversed-phase thin-layer chromatography and ultra-performance liquid chromatography/mass spectrometry to estimate the drug likeness of phosphodiesterase 10A inhibitors with phthalimide core

Lipophilicity is a physicochemical parameter well known as a decisive factor for predicting the successful development of a drug. Thus, a balance between potency and physicochemical properties during medicinal chemistry optimization is needed. In this study, the lipophilicity of isoindole-1,3(2H)-dione derivatives designed as phosphodiesterase 10A (PDE10A) inhibitors was determined by chromatographic [reversed-phase thin-layer chromatography (RP-TLC) and ultra-performance liquid chromatography/mass spectrometry (UPLC/MS)] and in silico methods. To assess the correlation between the obtained lipophilicity parameters, principal component analysis (PCA) was performed. logP values obtained by chromatographic (logPRP-TLC and logPUPLC/MS) and in silico methods were compared using the PCA method. The results of PCA revealed that logPUPLC/MS and in silico clogP provided by the ChemDraw program were highly correlated. Compounds’ drug likeness was screened, and the pharmacokinetic properties were predicted. All the investigated compounds displayed drug-likeness properties, and they met the criteria of Lipinski’s rule of five, which predicted the oral bioavailability of drug candidates. Analysis of the influence of physicochemical properties on the biological activity showed that the compounds with increased potency on PDE10A had significantly higher topological polar surface area (TPSA) values. The blood‒brain barrier permeability and the hemolytic activity of model compound 18 were examined. The model compound 18 displayed no toxicity effect on erythrocytes in the hemolytic assay and good parallel artificial membrane permeability. The results showed that phthalimide compounds with benzimidazole moiety are a source of compound-targeted inhibition of PDE10A with balanced physicochemical and drug-likeness properties.

QSRR modeling of lipophilicity of new spirohydantoin derivatives determined with various TLC systems.

A Quantitative structure-retention relationship (QSRR) analysis has been carried out on the chromatography parameters of lipophilicity of selected spirohydantoins. Multiple linear regression (MLR) was applied for construct the QSRR models. The chromatographic parameters of lipophilicity were determined by reversed-phase thin-layer chromatography. Chromatographic analyses were performed on C-18 modified silica gel with a two-component mobile phase consisting of water and protic organic solvent (ethanol, n-propanol, i-propanol, or t-butanol) in different ratios. QSRR models were built and for additional four aqueous mobile phases: acetone-water, acetonitrile-water, tetrahydrofuran-water, and 1,4-dioxane-water (results published before). In total, chromatographic lipophilicity parameters obtained for two types of organic solvents was subject of the QSRR. The predictive ability of each model was defined by an internal validation coefficient. The best QSRR model for predicting the chromatographic parameter of lipophilicity was obtained for tetrahydrofuran as an organic solvent.

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

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 RM 0, 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.

Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives.

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between -1.25 and -0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

Application of high sensitive silver nanocubes SERS substrate for detection of metribuzin

Metribuzin, which is a triazinone herbicide, is extensively used in agricultural activities in order to control the spread of broad leaved weeds and grasses. This herbicide is treated as a hazardous chemical, since it multiplies the contamination in the ecosystem by infiltrating to groundwater and soil layers. Thus, detection of Metribuzin in even low concentrations is of vital importance. To date, analytical methods such as High Performance Liquid Chromatography (HPLC), reversed-phase thin-layer chromatography (RP-TLC) with UV absorption detection, Gas chromatography, and Mass spectrometry were utilized in order to detect Metribuzin. At this point, Surface Enhanced Raman Spectroscopy (SERS), while being not as analytical as the methods discussed above, emerges as a significant alternative, since it requires almost no consumables, requires a very short time for analysis and it allows on site analysis. In this study Ag nanocubes were synthesized as a SERS substrate and They were utilized for detection of Metribuzin at concentrations from 10−3 to 10−10 M. Reproducibility, sensitivity and chemical stability tests exhibited that Ag nanocubes were excellent candidates of SERS substrates by allowing detection at ultra- low concentrations up to 10−10 M.

Evaluation of the Effect of Betulin and Its Alkynyl Derivatives on the Profile of Changes in Gene Expression of the Inflammatory Process of Colorectal Adenocarcinoma Cells (HT-29 Cell Line)

Betulin is a lupane-type pentacyclic triterpene. It is characterized by a range of biological properties, including anti-cancer and anti-inflammatory activities. It is also an origin compound for obtaining derivatives with higher biological activity and better bioavailability. Chronic inflammation stimulates the formation of a pro-cancer microenvironment, promoting tumor growth, cell migration, and neoangiogenesis. Many factors, immune system cells, and cytokines and chemokines released by them are involved in this process. Therefore, it has been suggested that the optimal target for anti-cancer drugs in this disease could be substances showing anti-inflammatory activity. The aim of the study was to indicate the direction of changes in the expression of genes related to the inflammatory state in colorectal cancer cells promoted by betulin and its selected alkynyl derivatives. Cytotoxicity assessment was carried out using a sulforhodamine B (SRB) test, whereas lipophilicity was determined by reversed-phase thin-layer chromatography (RP-TLC). The analysis of the gene expression profile in colon adenocarcinoma cells treated with betulin and its derivatives was performed using oligonucleotide microarrays HG-U133A. Based on the conducted analysis, it can be stated that betulin and its derivatives 1–3 influence the change in the expression profile of genes related to inflammatory processes in the HT-29 colon adenocarcinoma cell lines. The highest expression changes (FC > 2) were observed for HMOX1 (compound 1 vs. control) and TMED7 (compound 3 vs. control) mRNAs. An important observation is the comparison of the profile of changes in the expression of the studied genes in the compared compounds. Derivative 1 showed the greatest similarity to control cells, whereas betulin showed similarity to cisplatin. These observations indicate the necessity further research on the impact of betulin and its derivatives on inflammatory processes and the possible direction of chemical modification of compounds.

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives.

Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log kw, RM0). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski's rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates.

Study on binding affinity profile, bioactivity, and lipophilicity of selected antipsychotic drugs

Schizophrenia is a complex mental illness that affects almost 1% of the population and has no curative treatment. Currently, available neuroleptic drugs have severe limitations and induce drug-related adverse effects. Receptor binding affinity parameters and lipophilicity are important characteristics that describe the bioactivity of these drugs. Lipophilicity is an important physicochemical property of a drug, which predicts distribution, binding to plasma protein, crossing the blood–brain barrier, and biological activity. Five antipsychotic drugs (Haloperidol, Risperidone, Aripiprazole, Olanzapine, and Quetiapine) were selected and the experimental determination of lipophilicity was carried out by reverse phase thin-layer chromatography (RP-TLC) using four types of stationary phases (RP-18, CN, Diol, and NH2 modified silica gel HPTLC plates) and acetonitrile-water with increasing percentage of acetonitrile and 0.2% formic acid in each case as mobile phase. Lipophilicity parameters (mRM and RM0) calculated from the experimental chromatographic retention data were discussed in terms of the correlation with different receptor binding affinity parameters determined by computational methods.

Quorum sensing activities and genomic insights of plant growth-promoting rhizobacteria isolated from Assam tea.

Secretion of quorum sensing (QS) molecules is important for the effective colonization of host plants by plant growth-promoting rhizobacteria. The current study aims at the isolation and characterization of tea rhizo bacteria, which produce the QS molecules, acyl homoserine lactone (AHLs), along with multiple plant growth-promoting (PGP) activities. Thirty-one isolates were isolated from the tea rhizosphere, and screening for PGP activities resulted in the selection of isolates RTE1 and RTE4 with multiple PGP traits, inhibiting the growth of tea fungal pathogens. Both isolates also showed production of AHL molecules when screened using two biosensor strains, Chromobacterium violaceum CV026 and Escherichia coli MT 102(jb132). The isolates identified as Burkholderia cepacia RTE1 and Pseudomonas aeruginosa RTE4 based on genome-based analysis like phylogeny, dDDH, and fastANI calculation. Detailed characterization of AHLs produced by the isolates using reverse-phase TLC, fluorometry, and LC-MS indicated that the isolate RTE1 produced a short chain, C8, and a long chain C12 AHL, while RTE4 produced short-chain AHLs C4 and C6. Confocal microscopy revealed the formation of thick biofilm by RTE1 and RTE4 (18 and 23μm, respectively). Additionally, we found several genes involved in QS, and PGP, inducing systemic resistance (ISR) activities such as lasI/R, qscR, pqq, pvd, aldH, acdS, phz, Sod, rml, and Pch, and biosynthetic gene clusters like N-acyl homoserine lactone synthase, terpenes, pyochelin, and pyocyanin. Based on the functional traits like PGP, biofilm formation and production of AHL molecules, and genetic potential of the isolates B. cepacia RTE1 and P. aeruginosa RTE4 appear promising candidates to improve the health and growth of tea plantations.

Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action.

Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski's rule of five, Ghose's, and Veber's rules were checked for the tested compounds, confirming their bioavailability.

SCREENING OF MARINE BACTERIUM VIBRIO ALGINOLYTICUS STRAIN AS05 FOR THE PRODUCTION OF N-ACYL HOMOSERINE LACTONE-BASED QUORUM SENSING SIGNALING MOLECULES

Marine environments, including aquatic and coastal environments, are highly prevalent of marine bacteria with the highest levels of Vibrio species. Vibrios play a vital role in marine ecology associated with carbon and energy acquisition. The density-dependent quorum sensing (QS) system may regulate certain biological activities in marine bacteria. QS is a conversation system utilized by many bacterial communities to communicate and coordinate through different signalling molecules. N-acyl homoserine lactones (AHLs) are the most important QS signalling molecules widely produced by Gram-negative bacteria. This study aimed to investigate the detection and Identification of AHL-based QS signalling molecules produced by marine bacterium V. alginolyticus strain AS05 isolated from marine water of the Arabian Sea, Karachi, Pakistan. Marine medium Zobell-2216 was used to isolate bacterial strains. Moreover, 16S rRNA analysis was applied to identify AS05 strain. Agar plate bioassay was used to detect the production of AHL signalling molecules using Chromobacterium violaceum CV026 as a biosensor. The Identification of AHLs was made by reversed-phase thin-layer chromatography (RP-TLC) analysis. The NCBI-blast results revealed the identification of the isolated bacterial strain as Vibrio alginolyticus strain AS05 (OQ130030) member of the family of Vibrionaceae under the class of Gammaproteobacteria. The results of agar plate bioassay using CV026 as a biosensor strain revealed highly positive reactions for producing AHL signalling molecules. Moreover, two AHL molecules produced by AS05 bacterial strain were identified as C6-HSL and C-8HSL based on TLC analysis. This study reveals the detection and Identification of two different AHL signalling molecules produced by V. alginolyticus AS05 isolated from marine water of the Arabian Sea, Karachi, Pakistan. This study provides insight into investigating quorum-sensing signalling molecules in the Arabian Sea, Karachi, Pakistan, and marine bacterial species.

Lipophilicity Study of Fumaric and Maleic Acids

The experimental lipophilicity of fumaric acid (FA) and maleic acid (MA) using the traditional shake-flask method in an n-octanol–water system using reversed-phase thin-layer chromatography (RP-TLC) was determined. Experimental partition coefficients (logPexp) were equal to −0.65 and 0.63 for MA and FA, respectively. The chromatographic lipophilicity (RMW) of the FA and MA was evaluated using reversed-phase thin-layer chromatography on RP8F254s, RP18WF254, and CNF254s plates with a mixture of an organic solvent (methanol or dioxane) and water as the mobile phase. All applied chromatographic conditions were appropriate to determine the lipophilicity of the tested MA and FA. Topological indices derived from distance matrices allowed for the development of a new method for the evaluation of the lipophilicity of MA and FA. All methods applied in this work indicate that MA is less lipophilic than FA. The methods used in this work to determine lipophilicity are of particular importance in the aspect of studying cis- and trans-configuration compounds, because generally available computer programs based on various algorithms (Virtual Computational Chemistry Laboratory and Molinspiration Cheminformatics) indicate that fumaric acid and maleic acid have identical logP values.

Computational Approach to Drug Penetration across the Blood-Brain and Blood-Milk Barrier Using Chromatographic Descriptors.

Drug penetration through biological barriers is an important aspect of pharmacokinetics. Although the structure of the blood-brain and blood-milk barriers is different, a connection can be found in the literature between drugs entering the central nervous system (CNS) and breast milk. This study was created to reveal such a relationship with the use of statistical modelling. The basic physicochemical properties of 37 active pharmaceutical compounds (APIs) and their chromatographic retention data (TLC and HPLC) were incorporated into calculations as molecular descriptors (MDs). Chromatography was performed in a thin layer format (TLC), where the plates were impregnated with bovine serum albumin to mimic plasma protein binding. Two columns were used in high performance liquid chromatography (HPLC): one with immobilized human serum albumin (HSA), and the other containing an immobilized artificial membrane (IAM). Statistical methods including multiple linear regression (MLR), cluster analysis (CA) and random forest regression (RF) were performed with satisfactory results: the MLR model explains 83% of the independent variable variability related to CNS bioavailability; while the RF model explains up to 87%. In both cases, the parameter related to breast milk penetration was included in the created models. A significant share of reversed-phase TLC retention values was also noticed in the RF model.