National Technical University of Athens, School of Chemical Engineering, Laboratory of Organic Chemistry, Zografou Campus, Athens 15773, Greece.
National Technical University of Athens, School of Chemical Engineering, Laboratory of Organic Chemistry, Zografou Campus, Athens 15773, Greece.
J Inorg Biochem. 2019 May;194:65-73. doi: 10.1016/j.jinorgbio.2019.02.008. Epub 2019 Feb 21.
This study aims at the further expansion of knowledge on the antimicrobial activities of the tetramic acid moiety and the effect of metal complexation. Complexes of the N-acetyl-3-acetyl-5-benzylidenetetramic acid with Mn, Co, Ni, Cu, Zn and Cd were synthesized and screened against 5 key ESKAPE pathogens (Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) and 2 fungi (Cryptococcus neoformans and Candida albicans). The cadmium complex was found to effectively inhibit the fungus Cryptococcus neoformans with minimum inhibitory concentration (MIC) of 8 μg/mL, with no human cell toxicity and hemolytic activity within the tested concentration range. The biologically active tetramic acid‑cadmium complex was structurally characterized by single-crystal X-ray analysis. Furthermore, the thermal stability of the ligand and the complexes was investigated along with NMR and EPR studies of the Cd(II) and Co(II) complexes respectively.
本研究旨在进一步拓展四氢酸部分的抗菌活性和金属络合效应的知识。合成了 N-乙酰基-3-乙酰基-5-亚苄基四氢酸与 Mn、Co、Ni、Cu、Zn 和 Cd 的配合物，并对 5 种关键 ESKAPE 病原体（大肠杆菌、耐甲氧西林金黄色葡萄球菌（MRSA）、肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌）和 2 种真菌（新生隐球菌和白色念珠菌）进行了筛选。发现镉配合物能有效抑制真菌新生隐球菌，最小抑菌浓度（MIC）为 8μg/mL，在测试浓度范围内对人细胞无毒性和溶血活性。通过单晶 X 射线分析对具有生物活性的四氢酸-镉配合物进行了结构表征。此外，还研究了配体和配合物的热稳定性，以及分别对 Cd(II)和 Co(II)配合物进行了 NMR 和 EPR 研究。
