Abstract：
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.
摘要：
生殖支原体是在美国和全世界与泌尿生殖道疾病综合征相关的性传播细菌。生殖支原体耐药性的全球上升需要开发治疗这种病原体的新药。为了满足这一需求，我们从通过俄克拉荷马大学公民科学土壤收集计划组装的真菌分离株图书馆中筛选了提取物。使用生物测定指导的分级分离对一种生物活性提取物进行分析，从而纯化了化合物PF1140（1）以及一种新的和几种其他已知的吡啶酮。N-羟基吡啶酮通常被认为是在生理条件下对铁(III)具有高结合亲和力的铁载体。来自基于UV-vis吸收光谱的滴定实验的结果揭示了1与Fe3+的络合物。由于生殖支原体不利用铁，我们认为PF1140-铁复合物通过促进细胞摄取铁诱导细胞毒性，与内源性过氧化氢反应产生有毒的羟基自由基。
