An amidation/cyclization approach to the synthesis of N-hydroxyquinolinones and their biological evaluation as potential anti-plasmodial, anti-bacterial, and iron(II)-chelating agents

Bioorg Med Chem Lett. 2015 Feb 1;25(3):607-10. doi: 10.1016/j.bmcl.2014.12.014. Epub 2014 Dec 13.

Abstract

A 26-member library of novel N-hydroxyquinolinone derivatives was synthesized by a one-pot Buchwald-type palladium catalyzed amidation and condensation sequence. The design of these rare scaffolds was inspired from N-hydroxypyridones and 2-quinolinones classes of compounds which have been shown to have rich biological activities. The synthesized compounds were evaluated for their anti-plasmodial and anti-bacterial properties. In addition, these compounds were screened for their iron(II)-chelation properties. Notably, four of these compounds exhibited anti-plasmodial activities comparable to that of the natural product cordypyridone B.

Keywords: Anti-bacterial activity; Anti-plasmodial activity; Iron chelation; N-Hydroxyquinolinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Catalysis
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology
  • Cyclization
  • Escherichia coli / drug effects
  • Ferrous Compounds / chemistry*
  • Palladium / chemistry
  • Plasmodium / drug effects
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / pharmacology
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Bacterial Agents
  • Antimalarials
  • Chelating Agents
  • Ferrous Compounds
  • Quinolones
  • Palladium