Thilini Peramuna, Caroline M Kim, Laarni Kendra T Aguila, Karen L Wendt, Gwendolyn E Wood, Robert H Cichewicz
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引用次数: 0
摘要
生殖器支原体是一种性传播细菌,在美国和全世界都与泌尿生殖系统疾病综合征有关。生殖器支原体的耐药性在全球范围内呈上升趋势,因此有必要开发治疗这种病原体的新型药物。为了满足这一需求,我们对通过俄克拉荷马大学公民科学土壤收集计划收集的真菌分离物库中的提取物进行了筛选。使用生物测定指导分馏法对其中一种具有生物活性的提取物进行分析,最终纯化出了化合物 PF1140 (1),以及一种新的和其他几种已知的吡啶酮类化合物。在生理条件下,N-羟基吡啶酮通常被认为是对铁(III)具有高结合亲和力的苷元。基于紫外可见吸收光谱的滴定实验结果表明,1 与 Fe3+ 发生络合。由于 M. genitalium 不利用铁,我们认为 PF1140-铁复合物是通过促进细胞对铁的吸收来诱导细胞毒性的,铁与内源性过氧化氢反应产生有毒的羟自由基。
Iron(III) Binding Properties of PF1140, a Fungal N-Hydroxypyridone, and Activity against Mycoplasma genitalium.
Mycoplasma genitalium is a sexually transmitted bacterium associated with urogenital disease syndromes in the US and worldwide. The global rise in drug resistance in M. genitalium necessitates the development of novel drugs to treat this pathogen. To address this need, we have screened extracts from a library of fungal isolates assembled through the University of Oklahoma Citizen Science Soil Collection Program. Analysis of one of the bioactive extracts using bioassay-guided fractionation led to the purification of the compound PF1140 (1) along with a new and several other known pyridones. The N-hydroxy pyridones are generally regarded as siderophores with high binding affinity for iron(III) under physiological conditions. Results from UV-vis absorption spectroscopy-based titration experiments revealed that 1 complexes with Fe3+. As M. genitalium does not utilize iron, we propose that the PF1140-iron complex induces cytotoxicity by facilitating the cellular uptake of iron, which reacts with endogenous hydrogen peroxide to produce toxic hydroxyl radicals.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.