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

doi:10.1016/j.ejmech.2012.02.035

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 journal › Article › peer-review

37 Scopus citations

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 language	English (US)
Pages (from-to)	145-153
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	51
DOIs	https://doi.org/10.1016/j.ejmech.2012.02.035
State	Published - May 2012
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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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.",

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

author = "Dewal, {Mahender B.} and Wani, {Amit S.} and Celine Vidaillac and David Oupick{\'y} and Rybak, {Michael J.} and Firestine, {Steven M.}",

year = "2012",

month = may,

doi = "10.1016/j.ejmech.2012.02.035",

language = "English (US)",

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AU - Dewal, Mahender B.

AU - Wani, Amit S.

AU - Vidaillac, Celine

AU - Oupický, David

AU - Rybak, Michael J.

AU - Firestine, Steven M.

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

KW - Antibacterial

KW - Antibiotic-resistant bacteria

KW - Heterocycle synthesis

KW - MRSA

KW - Thieno[2,3-d]pyrimidinediones

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