New Hydrophobicity Constants of Substituents in Pyrazine Rings Derived from RP-HPLC Study

Kučerová-Chlupáčová, Marta; Opletalová, Veronika; Jampílek, Josef; Dolezel, Jan; Dohnal, Jiří; Pour, Milan; Kuneš, Jiřı́; Voříšek, Viktor

doi:10.1135/cccc20080001

Cited by 18 publications

(21 citation statements)

References 55 publications

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“…The obtained results of cytotoxicity correlate with the log k and Clog P parameters calculated in the work of Pospisilova et al [25]-the higher values of log k and Clog P parameters are, the higher IC 50 values are, for example, compound 6 (log k = 0.4859, IC 50 = 11.60 µM) >>>> compound 10 (log k = 0.6821, IC 50 = 6.28 µM) >> compound 11 (log k = 0.8155, IC 50 = 2.43 µM) ≈ compound 13 (log k = 0.9814, IC 50 = 2.17 µM). Naturally, these observations correspond with distributive parameters π (see Table 3), a constant characterizing hydrophobicity (lipophilicity contribution) of individual moieties, substituents, and substructures in some skeleton [31,32]; compound 6 (π Ar = 2.73) >>>> compound 10 (π Ar = 2.77) >> compound 11 (π Ar = 2.90) ≈ compound 13 (π Ar = 3.98). Nevertheless, di-substitution with highly lipophilic and electron-withdrawing substituents (Cl or CF 3 ) on the C (3,5) or C (3,4) positions of the anilide ring seems to be the most important for achieving a high antiproliferative effect.…”

Section: In Vitro Cell Viability Assaymentioning

confidence: 64%

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

et al. 2019

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A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)-3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C (2,5) or C (2,6) positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.Molecules 2019, 24, 4531 2 of 15 drugs are directly obtained from plants or fungi or are "nature-inspired" [11]. One such molecule is cinnamic acid (CA). It is a small organic molecule, which can be found in many kinds of plants in pure form or as a part of more complicated structures. CA and its natural and synthetic derivatives possess many interesting biological effects, such as antimicrobial [12,13], anticancer [14], anti-oxidant [13], and anti-inflammatory activities [15].N-Arylcinnamides represent a group of synthetic derivatives of CA. This group of compounds possesses several potentially active moieties-styryl, amide (peptide-like [16]) bond, and aryl [17][18][19][20][21][22]. Thus, cinnamides can be considered as a privilege structure or a scaffold (a part) of more complex molecules in medicinal chemistry [23,24] The series of N-arylcinnamide derivatives presented in this work was previously tested for their anti-microbial activity (compounds 1-15 and 17) [25,26], and three new derivatives 16 and 18 were prepared and characterized. Based on the concepts of polypharmacology, multifactorial diseases, and multitarget drugs [27], as well as the above-mentioned results, a group of eighteen N-arylcinnamanilides was chosen for the screening of their ability to moderate the inflammation-like reaction in vitro. Results and Discussion ChemistryThe investigated compounds (previously published compounds 1-15 and 17 [25] and two new compounds, 16 and 18) were prepared using a one-step microwave-assisted synthesis, see Scheme 1. Briefly, the carboxyl group of CA was activated with phosphorus trichloride, and then...

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Section: In Vitro Cell Viability Assaymentioning

confidence: 64%

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

et al. 2019

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“…Described (2E)-N-phenyl-3-phenylprop-2-enamide (1) was characterized recently by Pospisilova et al [10]. (2E)-3-Phenyl-N- (3,4,5-trichlorophenyl)prop-2-enamide (5). Yield 75%; Mp 247.9 °C; IR (cm −1 ): 3157,3080,1655,1613,1583,1513,1433,1378,1337,1281,1245,1196,1188,1148,1011,998,967,944,880,860,815,762,711,685,617,602,575,536…”

Section: Synthesismentioning

confidence: 99%

“…Therefore, reversed-phase high performance liquid chromatography (RP-HPLC) methods have become popular and widely used for lipophilicity measurement. A general procedure is the measurement of directly accessible retention time under isocratic conditions with varying amounts of an organic modifier in the mobile phase using end-capped non-polar C18 stationary RP columns and calculating the capacity factor k [4][5][6][7][8][9]. Log k, calculated from the capacity factor k, is used as the lipophilicity index converted to log P scale [4].…”

Section: Introductionmentioning

confidence: 99%

Preparation and Hydro-Lipophilic Properties of Selected Novel Chlorinated and Brominated N-Arylcinnamamides

Strhársky

Jankech

Kos

et al. 2019

The 23rd International Electronic Conference on Synthetic Organic Chemistry

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A series of six di-and tri-halogenated N-arylcinnamanilides designed as anti-inflammatory and antimicrobial agents was prepared and characterized. Since it is known that lipophilicity significantly influences the biological activity of compounds, the hydro-lipophilic properties of these di-and tri-substituted N-arylcinnamanilides were investigated in the study. All the discussed derivatives of cinnamic acid were analyzed using the reversed-phase high performance liquid chromatography method to measure lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, the correlations between the logarithm of the capacity factor k and log P/Clog P values calculated in various ways as well as the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.

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“…Since it was found that the lipophilicity of these significantly biologically effective agents determined their activity, in this study hydrolipophilic properties of all three series are investigated. Thus this contribution is a follow-up work to the previous papers [5][6][7][8][15][16][17][18][19][20][21][22][23][24][25] aimed at the physicochemical properties of new biologically active agents.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, reversed-phase high performance liquid chromatography (RP-HPLC) methods have become popular and widely used for lipophilicity measurement. A general procedure is the measurement of directly accessible retention time under isocratic conditions with varying amounts of an organic modifier in the mobile phase using end-capped non-polar C 18 stationary RP columns and calculating the capacity factor k [4][5][6][7][8]. Log k, calculated from the capacity factor k, is used as the lipophilicity index converted to log P scale [4].…”

Section: Introductionmentioning

confidence: 99%

Chromatographic and Computational Study of Hydro-lipophilic Properties of <em>N</em>-Alkoxyphenylhydroxy-naphthalenecarboxamides

Kapustíková

Goněc

Kos

et al. 2017

Proceedings of the 21st International Electronic Conference on Synthetic Organic Chemistry

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Abstract:N-Alkoxy-3-hydroxynaphthalene-2-carboxanilides, N-alkoxy-1-hydroxynaphthalene-2-carboxanilides and N-alkoxy-2-hydroxynaphthalene-1-carboxanilides were recently reported as series of compounds with antimycobacterial, antibacterial and herbicidal activity. As it was found that the lipophilicity of these significantly biologically effective agents determined their activity, in this study hydro-lipophilic properties of all three series are investigated. All fifty-seven anilides were analysed using the reversed-phase high performance liquid chromatography method for lipophilicity measurement. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C 18 stationary reversed-phase column. In the present study, the correlation between the logarithm of capacity factor k and log P/Clog P values calculated in various ways is discussed as well as the relationships between the lipophilicity and the chemical structure of the studied compounds.

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New Hydrophobicity Constants of Substituents in Pyrazine Rings Derived from RP-HPLC Study

Cited by 18 publications

References 55 publications

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

Preparation and Hydro-Lipophilic Properties of Selected Novel Chlorinated and Brominated N-Arylcinnamamides

Chromatographic and Computational Study of Hydro-lipophilic Properties of <em>N</em>-Alkoxyphenylhydroxy-naphthalenecarboxamides

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