Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN, 46556, USA.
Bioorg Med Chem. 2012 Jun 15;20(12):3828-36. doi: 10.1016/j.bmc.2012.04.034. Epub 2012 May 2.
Two desferrioxamine B-ciprofloxacin conjugates with 'trimethyl-lock' based linkers that are designed to release the antibiotic after esterase or phosphatase-mediated hydrolysis were synthesized. The potential esterase-sensitive conjugate 13 displayed moderate to good antibacterial activities against selected ferrioxamine-utilizing bacteria, although the activities were lower than the parent drug ciprofloxacin. However, the potential phophatase-sensitive conjugate 23 was inactive against the same panel of organisms tested. These properties appeared to be related to the activating efficiency of the linker by the enzyme and to the outer membrane protein recognition of the chemically modified siderophore used in the conjugate.
合成了两种基于“三甲基锁”连接子的去铁胺 B-环丙沙星缀合物，设计用于在酯酶或磷酸酶介导的水解后释放抗生素。潜在的酯酶敏感缀合物 13 对选定的利用铁氧体胺的细菌表现出中等至良好的抗菌活性，尽管活性低于母体药物环丙沙星。然而，潜在的磷酸酶敏感缀合物 23 对测试的同一组生物体没有活性。这些性质似乎与酶对连接子的激活效率以及缀合物中使用的化学修饰的铁载体的外膜蛋白识别有关。
