Biological activities and ADMET-related properties of novel set of cinnamanilides

A series of nineteen novel ring-substituted N-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against Staphylococcus aureus as the reference strain, two clinical isolates of methicillin-resistant S. aureus (MRSA), and Mycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 M) againstMRSAisolates than the commonly used ampicillin (MIC 45.8 M). The screening of the cell viability was performed using THP1-Blue NF- B cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC50 6.5 M), none of the discussed compounds showed any significant cytotoxic e ect up to 20 M. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF- B activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pKa calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping

Preparation and Hydro-Lipophilic Properties of Novel Fluorinated Benzyl Carbamates of 4-Aminosalicylanilides

A series of seven fluorinated benzyl carbamates of 4-aminosalicylanilides and unsubstituted benzyl [3-hydroxy-4-(phenylcarbamoyl)phenyl]carbamate designed as agents with the expected anticholinesterase and anti-inflammatory activity were prepared and characterized. As lipophilicity significantly influences the biological activity of compounds, the hydro-lipophilic properties of these mono-, di-, and tri-substituted carbamates were investigated in this study. All the discussed derivatives of 4-{[(benzyloxy)carbonyl]amino}-2-hydroxybenzoic acid were analyzed using reversed-phase high performance liquid chromatography 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, the logarithm of the distributive parameter D at pH 7.4, 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

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

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

Practical sample pretreatment techniques coupled with capillary electrophoresis for real samples in complex matrices

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