Background

Microorganisms produce siderophores in order to scavenge iron from the environment and this study focuses on the characterization of the two siderophores secreted by Bacillus megaterium. The general biological properties and pharmacokinetics following oral application of these compounds are reported.

Methods

Under optimized culture conditions, the siderophores were harvested, purified by chromatography and identified using LC-MS and NMR. Two dihydroxamate siderophores were isolated, schizokinen (MW = 420) and schizokinen imide (MW = 402).

Results

Both compounds demonstrate strong antioxidant activity and were found to be relatively nontoxic to both human hepatocellular carcinoma (Huh7) and peripheral blood mononuclear cells. The siderophores possess a strong affinity for iron(III) and decrease the levels of the labile iron pool (LIP) in iron-loaded cells in a concentration-dependent manner. Schizokinen, was detected as both the free siderophore and the iron complex in the plasma and urine of rats after oral gavage.

Conclusions

However, the bioavailability was low and thus schizokinen, like deferoxamine, has no potential as an orally active iron chelator for the treatment of systemic iron overload.

General significance

By virtue of the high affinity of schizokinen for tribasic metals, this siderophore does have considerable potential for the chelation of gallium(III) and the development of clinical diagnostic reagents.

中文翻译：

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巨大芽孢杆菌产生的两种铁载体的表征：初步研究其作为治疗剂的潜力。

背景

微生物产生铁载体以清除环境中的铁，本研究着重于巨大芽孢杆菌分泌的两种铁载体的表征。报道了口服口服这些化合物后的一般生物学特性和药代动力学。

方法

在优化的培养条件下，收获铁载体，通过色谱法纯化，并使用LC-MS和NMR进行鉴定。分离出两种二异羟肟酸酯铁载体，即裂殖蛋白（MW = 420）和裂殖蛋白酰亚胺（MW = 402）。

结果

两种化合物均显示出强大的抗氧化活性，并且被发现对人肝细胞癌（Huh7）和外周血单核细胞均无毒。铁载体对铁（III）具有很强的亲和力，并以浓度依赖的方式降低了载铁细胞中不稳定铁池（LIP）的水平。口服强饲法后，鼠血浆和尿液中均检测到了裂殖蛋白，即游离铁载体和铁络合物。

结论

但是，生物利用度低，因此裂殖子激酶与去铁胺一样，没有潜力用作治疗全身性铁超负荷的口服活性铁螯合剂。

一般意义

由于裂殖素对三价金属具有高度亲和力，因此该铁载体确实具有螯合镓（III）和开发临床诊断试剂的巨大潜力。