Study of Iron Piperazine-Based Chelators as Potential Siderophore Mimetics
Gram-negative bacteria’s resistance such as <i>Pseudomonas aeruginosa</i> and the <i>Burkholderia</i> 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...
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| Main Authors: | , , , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2019-10-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Gram-negative bacteria’s resistance such as <i>Pseudomonas aeruginosa</i> and the <i>Burkholderia</i> 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 <i>Pseudomonas</i> sp, we have synthesized and studied two piperazine-based siderophore mimetics carrying either catecholate moieties (<b>1</b>) or hydroxypyridinone groups (<b>2</b>) 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. <b>1</b> possesses even a pFe value superior than those of pyoverdine, the <i>P. aeruginosa</i> endogenous siderophore, suggesting its potential ability to compete with it. At physiological pH, <b>1</b> forms mainly a 2:3 complex with iron, whereas two species are observed for <b>2</b>. Unfortunately, the corresponding Ga(III)-<b>1</b> and <b>2</b> complexes showed no antibacterial activity against <i>P. aeruginosa</i> DSM 1117 strain. The evaluation of their siderophore-like activity showed that <b>1</b> and <b>2</b> could be internalized by the bacteria. |
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| Item Description: | 1424-8247 10.3390/ph12040160 |