title: Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Mahender B
authors.initials: MB
authors.lastname: Dewal
authors.forename: Amit S
authors.initials: AS
authors.lastname: Wani
authors.forename: Celine
authors.initials: C
authors.lastname: Vidaillac
authors.forename: David
authors.initials: D
authors.lastname: Oupický
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
authors.forename: Steven M
authors.initials: SM
authors.lastname: Firestine
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D012756:Sheep
chemical_list: D000900:Anti-Bacterial Agents; D011744:Pyrimidinones; C542082:thieno(2,3-d)pyrimidin-4-one