Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia.
Int J Mol Sci. 2022 Mar 15;23(6):3159. doi: 10.3390/ijms23063159.
A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against and clinical isolates of methicillin-resistant (MRSA). (2)--[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series . (2)--[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2)-3-(3,4-dichlorophenyl)--[3-(trifluoromethyl)phenyl]prop-2-enamide, (2)-3-(3,4-dichloro- phenyl)--[4-(trifluoromethyl)phenyl]prop-2-enamide and (2)-3-(3,4-dichlorophenyl)- -[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series and in addition to activity against and MRSA were highly active against and vancomycin-resistant isolates and against fast-growing and against slow-growing , non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.
设计、合成并表征了一系列十八个 4-氯肉桂酰苯胺和十八个 3,4-二氯肉桂酰苯胺。所有化合物均针对革兰氏阳性菌和两种分枝杆菌菌株进行了活性评估。还评估了它们对癌细胞和原代哺乳动物细胞系的活力。实验测定了化合物的亲脂性，并将其与具有生物活性的制备衍生物的其他物理化学性质相关联。3,4-二氯肉桂酰苯胺比 4-氯肉桂酰苯胺具有更广泛的作用谱和更高的抗菌功效；然而，所有化合物都比临床使用的药物（氨苄西林、异烟肼、利福平）更有效或相当。在这 36 种化合物中，有 6 种衍生物对 和耐甲氧西林金黄色葡萄球菌（MRSA）的临床分离株具有亚微摩尔活性。在系列 中，（2）--[3,5-双（三氟甲基）苯基]-3-（4-氯苯基）丙烯酰胺的活性最强。（2）--[3,5-双（三氟甲基）苯基]-3-（3,4-二氯苯基）丙烯酰胺、（2）-3-（3,4-二氯苯基）-[3-（三氟甲基）苯基]丙烯酰胺、（2）-3-（3,4-二氯苯基）- [4-（三氟甲基）苯基]丙烯酰胺和（2）-3-（3,4-二氯苯基）- [4-（三氟甲氧基）苯基]丙烯酰胺在系列 和除了对 和 MRSA 的活性外，对 和万古霉素耐药 株以及快速生长的 和缓慢生长的 、非危害测试模型也具有高度活性。此外，上述最后三种化合物对原代猪单核细胞衍生的巨噬细胞显示出可忽略不计的细胞毒性。
