Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

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...

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Detalles Bibliográficos
Autores principales: Jarrad, Angie M., Karoli, Tomislav, Debnath, Anjan, Tay, Chin Yen, Huang, Johnny X., Kaeslin, Geraldine, Elliott, Alysha G., Miyamoto, Yukiko, Ramu, Soumya, Kavanagh, Angela M., Zuegg, Johannes, Eckmann, Lars, Blaskovich, Mark A.T., Cooper, Matthew A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editions Scientifiques Elsevier 2015
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550478/
https://www.ncbi.nlm.nih.gov/pubmed/26117821
http://dx.doi.org/10.1016/j.ejmech.2015.06.019
Descripción
Sumario: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.

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