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

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2504-2512. doi: 10.1016/j.bmcl.2018.05.058. Epub 2018 May 30.

Abstract

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.

Keywords: 3-Hydroxypyridinone; Antimicrobial activity; Dendrimer; Hexadentate; Iron chelator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Dose-Response Relationship, Drug
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Iron Chelating Agents / chemical synthesis
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyridones / chemical synthesis
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Dendrimers
  • Iron Chelating Agents
  • Pyridones