Chromatographic parameters as tools for predicting the biological activity of azo derivatives

Preliminary assessment of the bioactive profile of azo derivatives was performed applying drug-likeness rules. As the presumed criteria of lipophilicity chromatographic parameters (RM0, m and C0) were calculated in mixtures water/ methanol and water/ acetonitrile by using reversed phase thin-layer chromatography (RPTLC C18/ UV254s). The relationships between chromatographic parameters and relevant software parameters of biological activity of azo derivatives were examined by linear regression and by two multivariate methods. Good linear relationships for each applied system were obtained. The multivariate methods show similarity of the chromatographic parameters (RM0, C0) with standard measure of lipophilicity and pharmacokinetic predictors. The chromatographic parameter m obtained in the same conditions exhibits better agreement with the drug-likeness and toxicity parameters. On the values of azo derivatives’ bioactivity parameters the polarity of the substituent has higher impact than its electronic effects.

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Synthesis of arylacetic acids and their effect on activation of fibrinolysis. Quantitative relations between structure and biological activity

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19801401 ◽

1980 ◽

Vol 45 (5) ◽

pp. 1401-1409 ◽

Cited By ~ 12

Author(s):

Miroslav Kuchař ◽

Bohumila Brunová ◽

Zdeněk Roubal ◽

Jiří Schlanger ◽

Oldřich Němeček

Keyword(s):

Biological Activity ◽

Regression Analysis ◽

Active Site ◽

Reversed Phase ◽

Heat Denaturation ◽

Arylacetic Acids ◽

Layer Chromatography ◽

Derivatives Of ◽

Lipophilicity Parameters ◽

Hydrophobic Bonding

A series of arylacetic acids, III, has been prepared and evaluated for activation of fibrinolysis and inhibition of heat-denaturation of serum albumin. regression analysis revealed that either activity was influenced mainly by lipophilicity of the aromatic substituents. The graph showing activation of fibrinolysis by acids III takes a linear course up to a maximum, followed by a step decrease. Also included in the series are p-benzyloxy derivatives of the arylacetic acids. Their lipophilicity has been evaluated by thin-layer chromatography, the method of reversed phase being employed. However, the lipophilicity parameters thus obtained fail to describe the hydrophobic bonding of these derivatives to the active site; tabulated values of the parameter π were better in this respect.

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Comparison of the Utility of RP-TLC Technique and Different Computational Methods to Assess the Lipophilicity of Selected Antiparasitic, Antihypertensive, and Anti-inflammatory Drugs

Molecules ◽

10.3390/molecules24173187 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3187

Author(s):

Pyka-Pająk ◽

Parys ◽

Dołowy

Keyword(s):

Good Alternative ◽

Reversed Phase ◽

Biologically Active ◽

Chromatographic Parameter ◽

Acetone Water ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Antiparasitic Drugs ◽

Layer Chromatography ◽

Lipophilicity Parameters

The aim of this study was to assess the lipophilicity of selected antiparasitic, antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) by means of reversed phase–thin layer chromatography (RP-TLC) as well by using Soczewiński–Wachtmeister’s and J. Ościk’s equations. The lipophilicity parameters of all examined compounds obtained under various chromatographic systems (i.e., methanol-water and acetone-water, respectively) and those determined on the basis of Soczewiński-Wachtmeister’s and Ościk’s equations (i.e., RMWS and RMWO) were compared with the theoretical ones (e.g., AlogPs, AClogP, milogP, AlogP, MlogP, XlogP2, XlogP3) and the experimental value of the partition coefficient (logPexp). It was found that the RMWS parameter may be a good alternative tool in describing the lipophilic nature of biologically active compounds with a high and low lipophilicity (i.e., antihypertensive and antiparasitic drugs). Meanwhile, the RMWO was more suitable for compounds with a medium lipophilicity (i.e., non-steroidal anti-inflammatory drugs). The chromatographic parameter 0(a) can be helpful for the prediction of partition coefficients, i.e., AClogP, XlogP3, as well as logPexp of examined compounds.

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Multivariate Methods to Evaluate the Role of Mixed Supports in Reversed-Phase Thin-Layer Chromatography

Journal of Liquid Chromatography ◽

10.1080/01483918908051773 ◽

1989 ◽

Vol 12 (6) ◽

pp. 957-978 ◽

Cited By ~ 6

Author(s):

Gábor Gullner ◽

Tibor Cserháti ◽

Barna Bordás ◽

Klára Valkó

Keyword(s):

Thin Layer ◽

Thin Layer Chromatography ◽

Reversed Phase ◽

Multivariate Methods ◽

Layer Chromatography

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Lipophilicity Determination of Antifungal Isoxazolo[3,4-b]pyridin-3(1H)-ones and Their N1-Substituted Derivatives with Chromatographic and Computational Methods

Molecules ◽

10.3390/molecules24234311 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4311 ◽

Cited By ~ 2

Author(s):

Krzesimir Ciura ◽

Joanna Fedorowicz ◽

Filip Andrić ◽

Petar Žuvela ◽

Katarzyna Ewa Greber ◽

...

Keyword(s):

Biological Activity ◽

High Performance ◽

Density Functional ◽

Principal Component ◽

Reversed Phase ◽

Drug Candidate ◽

Antifungal Activities ◽

Physicochemical Descriptors ◽

Sum Of Ranking Differences ◽

Layer Chromatography

The lipophilicity of a molecule is a well-recognized as a crucial physicochemical factor that conditions the biological activity of a drug candidate. This study was aimed to evaluate the lipophilicity of isoxazolo[3,4-b]pyridine-3(1H)-ones and their N1-substituted derivatives, which demonstrated pronounced antifungal activities. Several methods, including reversed-phase thin layer chromatography (RP-TLC), reversed phase high-performance liquid chromatography (RP-HPLC), and micellar electrokinetic chromatography (MEKC), were employed. Furthermore, the calculated logP values were estimated using various freely and commercially available software packages and online platforms, as well as density functional theory computations (DFT). Similarities and dissimilarities between the determined lipophilicity indices were assessed using several chemometric approaches. Principal component analysis (PCA) indicated that other features beside lipophilicity affect antifungal activities of the investigated derivatives. Quantitative-structure-retention-relationship (QSRR) analysis by means of genetic algorithm—partial least squares (GA-PLS)—was implemented to rationalize the link between the physicochemical descriptors and lipophilicity. Among the studied compounds, structure 16 should be considered as the best starting structure for further studies, since it demonstrated the lowest lipophilic character within the series while retaining biological activity. Sum of ranking differences (SRD) analysis indicated that the chromatographic approach, regardless of the technique employed, should be considered as the best approach for lipophilicity assessment of isoxazolones.

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RETENTION BEHAVIOR AND BIOLOGICAL ACTIVITY OF N-SUBSTITUTED-2-PHENYLACETAMIDE DERIVATES

Contemporary Materials ◽

10.7251/comen1401124v ◽

2014 ◽

Vol 5 (1) ◽

Author(s):

Đenđi Vaštag ◽

Suzana Apostolov ◽

Borko Matijević ◽

Jelena Nakomčić ◽

Aleksandar Marinković

Keyword(s):

Biological Activity ◽

Biological Activities ◽

Biological Properties ◽

Reversed Phase ◽

Chromatographic Retention ◽

Wide Range ◽

Structure Retention ◽

The Mathematical Model ◽

The Relationship ◽

Layer Chromatography

Phenylacetamide derivatives are a group of compounds that exhibit a wide range of biological activities as analgetic, anticonvulsant, pesticide, cytostatic. It is well known that the biological activity and the field of activity of the substance are greatly dependent on its physical, chemical and structural properties. In this paper, we applied QSRR analysis (Quantitative Structure Retention Relationships), which is based on the prediction of biological properties of compounds based on their chromatographic retention behaviors. To that end, retention constants of investigated N-substituted-2-phenylacetamide were determined by reversed phase thin-layer chromatography, (HPTLC RP18 F254s) in the presence of different volume fractions of n-propanol and tetrahydrofuran. The resulting data were correlated with molecular descriptors determined in different ways in order to establish the mathematical model that describes the relationship between retention properties and biological activities of investigated phenylacetamides.

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STUDY OF THE BIOLOGICAL ACTIVITY DESCRIPTORS OF THE BARBITURIC ACID DERIVATIVES

Contemporary Materials ◽

10.7251/comen2002077a ◽

2020 ◽

Vol 11 (2) ◽

Author(s):

Suzana Apostolov ◽

Đenđi Vaštag ◽

Borko Matijević ◽

Gorana Mrđan ◽

Jelena Nakomčić

Keyword(s):

Biological Activity ◽

Barbituric Acid ◽

Linear Regression Analysis ◽

Reversed Phase ◽

Chromatographic Behavior ◽

Organic Modifiers ◽

Test Organisms ◽

The Central Nervous System ◽

Chromatographic Parameters ◽

Barbituric Acid Derivatives

Barbituric acid derivatives have been pharmacologically significant compounds for decades. The central nervous system effects are conditioned by the presence of the pyrimidine-trione ring and the nature of the substituent in position 5. Lipophilicity as one of the key molecular descriptors of biological activity for selected barbituric acid derivatives was determined experimentally, using reversed-phase thin layer chromatography (RP TLC18 F254s), in two solvent systems. The influence of the substituent’s nature and the effects of applied organic modifiers on the chromatographic behavior of the tested derivatives were examined. For the studied derivatives the values of the partition coefficient (logP) as a standard measure of lipophilicity and effective concentration (EC50) as a measure of acute toxicity for different test organisms were calculated applying the appropriate software packages. Dependence between the chromatographic parameters as assumed measures of lipophilicity and the software-derived biological activity parameters of the studied barbituric acid derivatives were studied by linear regression analysis.

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