Abstract:
The ability of bacteria to develop resistance to antimicrobial agents poses problems in the treatment of numerous bacterial infections. One method to circumvent permeability-mediated drug resistance involves the employment of the \'Trojan horse\' strategy. The Trojan horse concept involves the use of bacterial iron uptake systems to enter and kill bacteria. The siderophore-drug complex is recognized by specific siderophore receptors and is then actively transported across the outer membrane. The recently identified benefits of this strategy have led to the synthesis of a series of siderophore-based antibiotics. Several studies have shown that siderophore-drug conjugates make it possible to design antibiotics with improved cell transport and reduce the frequency of resistance mutants. Growing interest in siderophore-drug conjugates for the treatment of human diseases including iron overload, cancer, and malaria has driven the search for new siderophore-drug complexes. This strategy may have special importance for the development of iron oxide nanoparticle-based therapeutics.
摘要:
细菌产生抗微生物剂抗性的能力在许多细菌感染的治疗中造成问题。规避渗透性介导的耐药性的一种方法包括采用“特洛伊木马”策略。特洛伊木马概念涉及使用细菌铁摄取系统来进入和杀死细菌。铁载体-药物复合物被特定的铁载体受体识别,然后被主动转运穿过外膜。该策略的最近确定的益处导致了一系列基于铁载体的抗生素的合成。一些研究表明,铁载体-药物缀合物可以设计具有改善的细胞转运并降低抗性突变体的频率的抗生素。对用于治疗包括铁超负荷在内的人类疾病的铁载体-药物缀合物的兴趣与日俱增,癌症,疟疾推动了对新铁载体-药物复合物的寻找。该策略对于基于氧化铁纳米颗粒的治疗剂的开发可能具有特殊的重要性。