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Eur J Med Chem. 2015 Aug 28;101:96-102. doi: 10.1016/j.ejmech.2015.06.019. Epub 2015 Jun 18.

Metronidazole-triazole conjugates: activity against Clostridium difficile and parasites.

Author information

1
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
2
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
3
Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, 6099, Australia.
4
Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
5
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia. Electronic address: m.cooper@uq.edu.au.

Abstract

Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window.

KEYWORDS:

Anaerobe; Antibiotic; Click chemistry; Nitroimidazole

PMID:
26117821
PMCID:
PMC4550478
DOI:
10.1016/j.ejmech.2015.06.019
[Indexed for MEDLINE]
Free PMC Article

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