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 µM) against MRSA isolates than the commonly used ampicillin (MIC 45.8 µM). The screening of the cell viability was performed using THP1-Blue™ NF-κB cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC50 6.5 µM), none of the discussed compounds showed any significant cytotoxic effect up to 20 μM. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-κB 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.

Central Mining Institute Pl Gwarkow 1 40166 Katowice Poland

Department of Analytical Chemistry Faculty of Natural Sciences Comenius University Ilkovicova 6 84215 Bratislava Slovakia

Department of Chemistry University of Silesia Szkolna 9 40007 Katowice Poland

Faculty of Pharmacy Comenius University Odbojarov 10 83232 Bratislava Slovakia

Global Change Research Institute CAS Belidla 986 4a 60300 Brno Czech Republic

Regional Centre of Advanced Technologies and Materials Faculty of Science Palacky University Slechtitelu 27 78371 Olomouc Czech Republic

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Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides

Trifluoromethylcinnamanilide Michael Acceptors for Treatment of Resistant Bacterial Infections

Chemistry towards Biology-Instruct: Snapshot

Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides

Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides