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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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
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author 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.
author_facet 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.
author_sort Jarrad, Angie M.
collection PubMed
description 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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spelling pubmed-45504782015-09-22 Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites 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. Eur J Med Chem Research Paper 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. Editions Scientifiques Elsevier 2015-08-28 /pmc/articles/PMC4550478/ /pubmed/26117821 http://dx.doi.org/10.1016/j.ejmech.2015.06.019 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
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.
Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title_full Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title_fullStr Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title_full_unstemmed Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title_short Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
title_sort metronidazole-triazole conjugates: activity against clostridium difficile and parasites
topic Research Paper
url 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
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