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咪唑-硫代氨基脲衍生物作为具有抗生物膜活性的有效化合物。

Imidazole-Thiosemicarbazide Derivatives as Potent Anti- Compounds with Antibiofilm Activity.

机构信息

Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.

Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.

出版信息

Cells. 2021 Dec 9;10(12):3476. doi: 10.3390/cells10123476.

Abstract

() is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti- activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate -infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress biofilm formation was observed.

摘要

()是一种细胞内致病性细菌,也是结核病的病原体。这种疾病是最古老、最致命的细菌感染之一,在全球范围内,尤其是在中低收入国家,对健康、社会和经济构成了重大挑战。缺乏有效的疫苗、漫长而昂贵的药物治疗以及耐药结核菌株的快速传播,导致结核病重新成为一种全球大流行疾病。在这里,我们评估了新型咪唑-硫代半卡巴肼衍生物(ITD)对 感染的体外活性及其对分枝杆菌生物膜形成的影响。在细胞系和人单核细胞衍生的巨噬细胞(MDM)中进行了新化合物的细胞毒性研究。通过测定resazurin 的最小抑菌浓度、时间杀伤曲线、细菌细胞内生长和对生物膜形成的影响来评估 ITD 的抗 活性。对耐药 ITD 突变体进行了突变频率和全基因组测序。具有穿透感染人巨噬细胞的能力并能显著抑制结核分枝杆菌的细胞内生长和抑制 生物膜形成的 ITD 具有抗分枝杆菌的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/8700351/e18713588358/cells-10-03476-g001.jpg

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