Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Biochim Biophys Acta Gen Subj. 2020 Oct;1864(10):129670. doi: 10.1016/j.bbagen.2020.129670. Epub 2020 Jun 19.
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.
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).
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.
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.
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.
微生物会产生铁载体以从环境中摄取铁，本研究专注于描述解淀粉芽孢杆菌分泌的两种铁载体的特性。报告了这些化合物经口服应用后的一般生物学特性和药代动力学。
在优化的培养条件下，收获铁载体，通过色谱法进行纯化，并使用 LC-MS 和 NMR 进行鉴定。分离出两种二羟肟酸铁载体，即裂合霉素（MW=420）和裂合霉素亚胺（MW=402）。
两种化合物均表现出较强的抗氧化活性，且对人肝癌细胞（Huh7）和外周血单核细胞均相对无毒。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负载铁细胞中不稳定铁池（LIP）的水平。裂合霉素在口服灌胃后的大鼠血浆和尿液中均以游离铁载体和铁复合物的形式被检测到。
然而，生物利用度较低，因此裂合霉素与去铁胺一样，没有作为治疗全身铁过载的口服活性铁螯合剂的潜力。
由于裂合霉素对三价金属的高亲和力，这种铁载体确实具有螯合镓（III）和开发临床诊断试剂的相当大的潜力。
