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

Mahender B. Dewal, Amit S. Wani, Celine Vidaillac, David Oupický, Michael J. Rybak, Steven M. Firestine

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume51
DOIs
StatePublished - May 1 2012

Fingerprint

Vancomycin
Anti-Bacterial Agents
Derivatives
Methicillin Resistance
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus
Methicillin
Pathogens
Cytotoxicity
Scaffolds
Toxicity
Cells
Pharmaceutical Preparations
Vancomycin-Resistant Enterococci

Keywords

  • Antibacterial
  • Antibiotic-resistant bacteria
  • Heterocycle synthesis
  • MRSA
  • Thieno[2,3-d]pyrimidinediones

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents. / Dewal, Mahender B.; Wani, Amit S.; Vidaillac, Celine; Oupický, David; Rybak, Michael J.; Firestine, Steven M.

In: European Journal of Medicinal Chemistry, Vol. 51, 01.05.2012, p. 145-153.

Research output: Contribution to journalArticle

Dewal, Mahender B. ; Wani, Amit S. ; Vidaillac, Celine ; Oupický, David ; Rybak, Michael J. ; Firestine, Steven M. / Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents. In: European Journal of Medicinal Chemistry. 2012 ; Vol. 51. pp. 145-153.
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