Study of Iron Piperazine-Based Chelators as Potential Siderophore Mimetics.

Gram-negative bacteria's resistance such as and the group to conventional antibiotics leads to therapeutic failure. Use of siderophores as Trojan horses to internalize antibacterial agents or toxic metals within bacteria is a promising strategy to overcome resistance phenomenon. To combat the sp, we have synthesized and studied two piperazine-based siderophore mimetics carrying either catecholate moieties () or hydroxypyridinone groups () as iron chelators. These siderophore-like molecules were prepared in no more than four steps with good global yields. The physicochemical study has highlighted a strong iron affinity since their pFe values were higher than 20. possesses even a pFe value superior than those of pyoverdine, the endogenous siderophore, suggesting its potential ability to compete with it. At physiological pH, forms mainly a 2:3 complex with iron, whereas two species are observed for . Unfortunately, the corresponding Ga(III)- and complexes showed no antibacterial activity against DSM 1117 strain. The evaluation of their siderophore-like activity showed that and could be internalized by the bacteria.