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

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.

Graphical AbstractThieno[2,3-d]pyrimidinedione derivatives have been synthesized and examined for antibacterial activity against Gram-positive and Gram-negative pathogens. Two compounds displayed potent activity (2–16 mg/L) against MRSA, VISA, VRSA and VRE.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Four unique thieno[2,3-d]pyrimidinediones were synthesized by a unique route. ► Two compounds displayed potent activity against antibiotic-resistant Gram-positive bacteria. ► One compound was selectively cytotoxic to bacteria and displayed no hemolytic activity.