Synthesis, iron binding and antimicrobial properties of hexadentate 3-hydroxypyridinones-terminated dendrimers

• Published in: Bioorganic & medicinal chemistry letters 2018-08, Vol.28 (14), p.2504-2512
• Main Authors: Zhou, Tao, Chen, Kai, Kong, Li-Min, Liu, Mu-Song, Ma, Yong-Min, Xie, Yuan-Yuan, Hider, Robert C.
• Format: Article
• Language: English
• Subjects: 3-Hydroxypyridinone; Antimicrobial activity; Dendrimer; Hexadentate; Iron chelator
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.05.058

[Display omitted] •Four novel hexadentate hydroxypyridinone-based dendrimers were prepared.•These dendrimer were found to possess high iron(III) binding affinity.•Such dendrimeric chelators exhibited marked antibacterial activity. Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric chelators were synthesized using a convergent strategy. Their iron chelating ability was demonstrated by UV/Visible spectrometry and high resolution mass spectrometry (HRMS). The iron binding affinities were also investigated by the competition with a fluorescent iron chelator CP691. The result indicated that these dendrimers possesses a high affinity for iron with a very high pFe3+ value, which is close to that of an isolated hexadentate unit. These dendrimeric chelators were found to exhibit inhibitory effect on the growth of both Gram-positive and Gram-negative bacteria.