Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents

Eur J Med Chem. 2012 May;51:145-53. doi: 10.1016/j.ejmech.2012.02.035. Epub 2012 Feb 25.

Abstract

Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for antibacterial activity against a range of gram-positive and gram-negative pathogens. Two compounds displayed potent activity (2-16 mg/L) against multi-drug resistant gram-positive organisms, including methicillin resistant, vancomycin-intermediate, vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and vancomycin-resistant enterococci (VRE). Only one of these agents possessed moderate activity (16-32 mg/L) against gram-negative strains. An examination of the cytotoxicity of these agents revealed that they displayed low toxicity (40-50 mg/L) against mammalian cells and very low hemolytic activity (2-7%). Taken together, these studies suggest that thieno[2,3-d]pyrimidinediones are interesting scaffolds for the development of novel gram-positive antibacterial agents.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Bacteria / drug effects*
  • Hemolysis / drug effects
  • Mice
  • NIH 3T3 Cells
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology*
  • Pyrimidinones / toxicity
  • Sheep

Substances

  • Anti-Bacterial Agents
  • Pyrimidinones
  • thieno(2,3-d)pyrimidin-4-one