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

Verbal, Facial and Autonomic Responses to Empathy-Eliciting Film Clips by Disruptive Male Adolescents with High Versus Low Callous-Unemotional Traits

This study examined empathy-related responding in male adolescents with disruptive behavior disorder (DBD), high or low on callous-unemotional (CU) traits. Facial electromyographic (EMG) and heart rate (HR) responses were monitored during exposure to empathy-inducing film clips portraying sadness, anger or happiness. Self-reports were assessed afterward. In agreement with expectations, DBD adolescents with high CU traits showed significantly lower levels of empathic sadness than healthy controls across all response systems. Between DBD subgroups significant differences emerged at the level of autonomic (not verbal or facial) reactions to sadness, with high CU respondents showing less HR change from baseline than low CU respondents. The study also examined basal patterns of autonomic function. Resting HR was not different between groups, but resting respiratory sinus arrhythmia (RSA) was significantly lower in DBD adolescents with high CU traits compared to controls. Results support the notion that CU traits designate a distinct subgroup of DBD individuals

Stimuli responsive polymorphism of C12NO/DOPE/DNA\mathrm{C_{12}NO/DOPE/DNA} complexes: Effect of pH, tempertaure and composition

N$_{,}$N-dimethyldodecylamine-N-oxide (C12NO) is a surfactant that may exist either in a neutral or cationic protonated form depending on the pH of aqueous solutions. Using small angle X-ray diffraction (SAXD) we observe the rich structural polymorphism of pH responsive complexes prepared due to DNA interaction with C12NO/dioleoylphosphatidylethanolamine (DOPE) vesicles and discuss it in view of utilizing the surfactant for the gene delivery vector of a pH sensitive system. In neutral solutions, the DNA uptake is low, and a lamellar Lα phase formed by C12NO/DOPE is prevailing in the complexes at 0.2≤C12NO/DOPE0.5) stabilizes the LαC phase in C12NO/DOPE/DNA complexes and the distance between DNA strands (dDNA) is modulated by the pH value. Both the composition and pH affect the DNA binding in the complexes reaching up to ~95% of the DNA total amount at acidic conditions

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