Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, Slechtitelu 27, 78371 Olomouc, Czech Republic.
Department of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland.
Molecules. 2020 Sep 9;25(18):4121. doi: 10.3390/molecules25184121.
A series of nineteen novel ring-substituted -arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against as the reference strain, two clinical isolates of methicillin-resistant (MRSA), and . (2)--[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 (2)--(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC 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 pK 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.
合成并表征了一系列十九个新型环取代的芳基肉桂酰胺。所有研究的化合物均针对作为参考菌株、两种耐甲氧西林金黄色葡萄球菌（MRSA）的临床分离株以及进行了测试。(2)--[3-氟-4-（三氟甲基）苯基]-3-苯基丙烯酰胺对 MRSA 分离株的活性甚至更好（最低抑菌浓度（MIC）为 25.9 和 12.9 µM），优于常用的氨苄西林（MIC 为 45.8 µM）。使用 THP1-Blue™ NF-κB 细胞进行了细胞活力筛选，除了 (2)--(4-溴-3-氯苯基）-3-苯基丙烯酰胺（IC 6.5 µM）外，讨论的化合物在高达 20 µM 的浓度下均未显示出任何明显的细胞毒性作用。此外，所有化合物均进行了抗炎潜力测试；几种化合物减弱了脂多糖诱导的 NF-κB 激活，并且比母体肉桂酸更有效。还通过一组自由/商业 clogP 估算值进行了亲脂性值的计算，然后根据在生理 pH 下计算的相应 pK 值进行了校正，随后与实验参数进行了交叉比较。使用主成分分析、Tanimoto 度量和 Kohonen 映射对结构类似物进行了基于相似性的属性空间评估。
