Pospisilova Sarka, Michnova Hana, Kauerova Tereza, Pauk Karel, Kollar Peter, Vinsova Jarmila, Imramovsky Ales, Cizek Alois, Jampilek Josef
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia; Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic.
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic.
Bioorg Med Chem Lett. 2018 Jul 1;28(12):2184-2188. doi: 10.1016/j.bmcl.2018.05.011. Epub 2018 May 14.
A series of 13 salicylamide derivatives was assessed for antibacterial activity against three isolates of vancomycin-resistant Enterococcus faecalis (VRE) and Enterococcus faecalis ATCC 29212 as a quality standard. The minimum inhibitory concentration was determined by the broth microdilution method with subsequent subcultivation of aliquots to assess minimum bactericidal concentration. The growth kinetics was established by the time-kill assay. Ampicillin, ciprofloxacin, tetracycline and vancomycin were used as the reference antibacterial drugs. Three of the investigated compounds showed strong bacteriostatic activity against VRE (0.199-25 µM) comparable to or more potent than ampicillin and ciprofloxacin. In addition, these compounds were tested for synergistic effect with vancomycin, ciprofloxacin and tetracycline, while 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)phenyl]benzamide showed the highest potency as well as synergistic activity with vancomycin against VRE 368. Screening of the cytotoxicity of the most effective compounds was performed using human monocytic leukemia THP-1 cells, and based on LD values, it can be stated that the compounds have insignificant toxicity against human cells.
评估了一系列13种水杨酰胺衍生物对三株耐万古霉素粪肠球菌(VRE)和粪肠球菌ATCC 29212的抗菌活性,后者作为质量标准菌株。通过肉汤微量稀释法测定最低抑菌浓度,随后对等分试样进行继代培养以评估最低杀菌浓度。通过时间杀菌试验确定生长动力学。氨苄西林、环丙沙星、四环素和万古霉素用作参考抗菌药物。所研究的化合物中有三种对VRE显示出较强的抑菌活性(0.199 - 25µM),与氨苄西林和环丙沙星相当或更强。此外,测试了这些化合物与万古霉素、环丙沙星和四环素的协同作用,而5 - 氯 - 2 - 羟基 - N - [4 - (三氟甲基)苯基]苯甲酰胺对VRE 368显示出最高效力以及与万古霉素的协同活性。使用人单核细胞白血病THP - 1细胞对最有效化合物的细胞毒性进行筛选,基于半数致死量值,可以说这些化合物对人细胞的毒性不显著。