Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
J Pharm Biomed Anal. 2011 Apr 5;54(5):1047-58. doi: 10.1016/j.jpba.2010.12.016. Epub 2010 Dec 21.
Within the scope of searching for new lead structures in the field of anti-infectives, we ascertained Fenton's reagent to be an easy-to-handle and non-expensive tool for screening the metabolic profile of new bioactive compounds. The underlying chemistry of the Fenton's one-electron oxidation is comparable to that of cytochrome P450, which is the main metabolism enzyme. To study the metabolic screening capability, we subjected different antibiotics and the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A to Fenton's reagent and examined the obtained compound libraries by liquid chromatography/tandem mass spectrometry (LC-MS/MS). For ciprofloxacin and linezolid about half of literature-known metabolites were identified as products of Fenton's oxidation. For dioncophylline A six new possible metabolites were discovered.
在寻找抗感染领域新的先导结构的范围内，我们确定芬顿试剂是一种易于操作且廉价的工具，可用于筛选新生物活性化合物的代谢谱。芬顿试剂的单电子氧化的基础化学与细胞色素 P450 相当，细胞色素 P450 是主要的代谢酶。为了研究代谢筛选能力，我们将不同的抗生素和抗疟原虫的萘基异喹啉生物碱地奥可啉 A 用芬顿试剂处理，并通过液相色谱/串联质谱 (LC-MS/MS) 检查得到的化合物文库。对于环丙沙星和利奈唑胺，约有一半文献已知的代谢产物被鉴定为芬顿氧化的产物。对于地奥可啉 A，发现了六个新的可能代谢物。
