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

1980 ◽  
Vol 45 (5) ◽  
pp. 1401-1409 ◽  
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.

The melanocyte stimulating activity of N-nitroso-2-chloroethyl-carbamoyl derivatives of α-melanotropin fragments

1988 ◽  
Vol 53 (11) ◽  
pp. 2574-2582 ◽  
Author(s):  
Hedvig Medzihradszky-Schweiger ◽  
Helga Süli-Vargha ◽  
József Bódi ◽  
Kálmán Medzihradszky
Keyword(s):  
Biological Activity ◽  
Active Site ◽  
Frog Skin ◽  
Terminal Sequence ◽  
Subsequent Reaction ◽  
Affinity Labels ◽  
Derivatives Of

A number of N-nitroso-2-chloroethyl-carbamoyl (Q(NO)) derivatives of α-melanotropin fragments have been synthesized and their effect on the frog skin melanocytes studied. Peptides substituted in this way possess the biological activity of the parent compounds, indicating that they preserved their receptor recognizing ability. These compounds can therefore serve as affinity labels. Some of these derivatives, related to the C-terminal sequence of α-melanotropin show prolonged darkening reaction, which does not influence the subsequent reaction of melanocytes with α-melanotropin. The Q(NO)-derivative of a fragment derived from the classical active site of the hormone shows, however, inhibition of the effect of α-melanotropin. It can be concluded that the latter peptide acts through the melanotropin receptor, while others, related to the C-terminal sequence of the hormone through another mechanism.

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

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Suzana Apostolov ◽  
Gyöngyi Vastag
Keyword(s):  
Biological Activity ◽  
Reversed Phase ◽  
Multivariate Methods ◽  
Electronic Effects ◽  
Preliminary Assessment ◽  
Linear Relationships ◽  
Chromatographic Parameter ◽  
Azo Derivatives ◽  
Chromatographic Parameters ◽  
Layer Chromatography

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.

scholarly journals Evidence of changes in hydrophilic/hydrophobic balance and in chemical activity of HSA induced by thermal treatments

2011 ◽  
Vol 9 (2) ◽  
pp. 245-252 ◽  
Author(s):  
Victor Sahini ◽  
Gabriela Ionita
Keyword(s):  
Free Radical ◽  
Sodium Dodecyl ◽  
Reversed Phase ◽  
Water Soluble ◽  
Heat Denaturation ◽  
Thermal Treatments ◽  
Paramagnetic Resonance ◽  
Kinetic Measurements ◽  
Electron Paramagnetic ◽  
Layer Chromatography

AbstractSamples of human serum albumin (HSA) obtained as a result of heat denaturation followed by refolding controlled by a cooling of the protein solution were studied by several methods: chromatographic measurements, kinetic of the reaction with a water soluble free radical and by electron paramagnetic resonance (EPR) spectroscopy. In this context the interaction of this protein with β-cyclodextrin (β-CD) and sodium dodecyl sulfate (SDS) was also investigated. Reversed phase thin layer chromatography (RP-TLC) showed changes in lipophylicity of HSA, which are related with the existence of different ensembles of conformers. The UV-Vis absorption spectra had shown the broadening of absorption band of the protein and a hyperchrom effect in the presence of SDS; β-CD reduces the effect of SDS on protein UV-Vis spectra.Kinetic measurements related to the reaction of HSA with a water soluble DPPH type free radical provided evidence that reactivity of the HSA denaturated conformers is higher compared with the natural conformer. The affinity of SDS to the albumins surface and the effect of β-CD on the SDS/protein aggregates were also evident by changes in the EPR spectra of the spin probe CAT16.

scholarly journals Reversed-phase thin-layer chromatography of some angiotensin converting enzyme (ACE) inhibitors and their active metabolites

2006 ◽  
Vol 71 (6) ◽  
pp. 621-628 ◽  
Author(s):  
Jadranka Odovic ◽  
Biljana Stojimirovic ◽  
Mirjana Aleksic ◽  
Dusanka Milojkovic-Opsenica ◽  
Zivoslav Tesic
Keyword(s):  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Ace Inhibitors ◽  
Reversed Phase ◽  
Log P ◽  
Binary Solvent ◽  
Active Metabolites ◽  
Solvent Systems ◽  
Layer Chromatography ◽  
Lipophilicity Parameters

The chromatographic behaviour of some ACE inhibitors and their active metabolites was examined under conditions of reversed-phase thin-layer chromatography on RP-18 silica using water-methanol, water-ethanol and water-acetone as binary solvent systems. The relationship between the R M values and the concentration of organic modifier in the mobile phases was linear. It was found that an increase in the content of the organicmodifier in the employed solvent systems led to a decrease of the R M values, i.e., of the retention. Also, the more hydrophobic compounds had a longer retention. Based on regression analysis of the plots, the lipophilicity parameters R M 0 and c 0 were calculated. The chromatographically obtained lipophilicity parameters were correlated with the calculated log P values.

scholarly journals 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 ◽  
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.

scholarly journals Pressurized planar electrochromatography of DNS amino acids derivatives in silica gel and silanized silica gel systems with formic acid addition to the water mobile phase

2021 ◽  
Author(s):  
Adam Chomicki ◽  
Tadeusz H. Dzido
Keyword(s):  
Amino Acids ◽  
Silica Gel ◽  
High Performance ◽  
Reversed Phase ◽  
Mobile Phases ◽  
Phase Systems ◽  
Silanized Silica ◽  
Layer Chromatography ◽  
Derivatives Of ◽  
Electrophoretic Effect

AbstractPressurized planar electrochromatography (PPEC) of dansyl (DNS) derivatives of amino acids in normal- and reversed-phase systems is presented. The results have been obtained for mobile phases with different acetonitrile (ACN) concentrations (0–85%). The data obtained show differences in separation selectivity between high-performance thin-layer chromatography (HPTLC) and PPEC systems. These differences originate from the electrophoretic effect which is involved in the PPEC system, contrary to the HPTLC one.

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

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4311 ◽  
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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