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Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases
Over 4.5 billion people are at risk of infection with soil transmitted helminths and there are concerns about the development of resistance to the handful of frontline nematocides in endemic populations. We investigated the anti-nematode efficacy of a series of polypyridylruthenium(II) complexes and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724747/ https://www.ncbi.nlm.nih.gov/pubmed/29207309 http://dx.doi.org/10.1016/j.ijpddr.2017.11.005 |
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author | Sundaraneedi, Madhu Eichenberger, Ramon M. Al-Hallaf, Rafid Yang, Dai Sotillo, Javier Rajan, Siji Wangchuk, Phurpa Giacomin, Paul R. Keene, F. Richard Loukas, Alex Collins, J. Grant Pearson, Mark S. |
author_facet | Sundaraneedi, Madhu Eichenberger, Ramon M. Al-Hallaf, Rafid Yang, Dai Sotillo, Javier Rajan, Siji Wangchuk, Phurpa Giacomin, Paul R. Keene, F. Richard Loukas, Alex Collins, J. Grant Pearson, Mark S. |
author_sort | Sundaraneedi, Madhu |
collection | PubMed |
description | Over 4.5 billion people are at risk of infection with soil transmitted helminths and there are concerns about the development of resistance to the handful of frontline nematocides in endemic populations. We investigated the anti-nematode efficacy of a series of polypyridylruthenium(II) complexes and showed they were active against L3 and adult stages of Trichuris muris, the rodent homologue of the causative agent of human trichuriasis, T. trichiura. One of the compounds, Rubb(12)-mono, which was among the most potent in its ability to kill L3 (IC(50) = 3.1 ± 0.4 μM) and adult (IC(50) = 5.2 ± 0.3 μM) stage worms was assessed for efficacy in a mouse model of trichuriasis by administering 3 consecutive daily oral doses of the drug 3 weeks post infection with the murine whipworm Trichuris muris. Mice treated with Rubb(12)-mono showed an average 66% reduction (P = 0.015) in faecal egg count over two independent trials. The drugs partially exerted their activity through inhibition of acetylcholinesterases, as worms treated in vitro and in vivo showed significant decreases in the activity of this class of enzymes. Our data show that ruthenium complexes are effective against T. muris, a model gastro-intestinal nematode and soil-transmitted helminth. Further, knowledge of the target of ruthenium drugs can facilitate modification of current compounds to identify analogues which are even more effective and selective against Trichuris and other helminths of human and veterinary importance. |
format | Online Article Text |
id | pubmed-5724747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57247472017-12-18 Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases Sundaraneedi, Madhu Eichenberger, Ramon M. Al-Hallaf, Rafid Yang, Dai Sotillo, Javier Rajan, Siji Wangchuk, Phurpa Giacomin, Paul R. Keene, F. Richard Loukas, Alex Collins, J. Grant Pearson, Mark S. Int J Parasitol Drugs Drug Resist Article Over 4.5 billion people are at risk of infection with soil transmitted helminths and there are concerns about the development of resistance to the handful of frontline nematocides in endemic populations. We investigated the anti-nematode efficacy of a series of polypyridylruthenium(II) complexes and showed they were active against L3 and adult stages of Trichuris muris, the rodent homologue of the causative agent of human trichuriasis, T. trichiura. One of the compounds, Rubb(12)-mono, which was among the most potent in its ability to kill L3 (IC(50) = 3.1 ± 0.4 μM) and adult (IC(50) = 5.2 ± 0.3 μM) stage worms was assessed for efficacy in a mouse model of trichuriasis by administering 3 consecutive daily oral doses of the drug 3 weeks post infection with the murine whipworm Trichuris muris. Mice treated with Rubb(12)-mono showed an average 66% reduction (P = 0.015) in faecal egg count over two independent trials. The drugs partially exerted their activity through inhibition of acetylcholinesterases, as worms treated in vitro and in vivo showed significant decreases in the activity of this class of enzymes. Our data show that ruthenium complexes are effective against T. muris, a model gastro-intestinal nematode and soil-transmitted helminth. Further, knowledge of the target of ruthenium drugs can facilitate modification of current compounds to identify analogues which are even more effective and selective against Trichuris and other helminths of human and veterinary importance. Elsevier 2017-11-29 /pmc/articles/PMC5724747/ /pubmed/29207309 http://dx.doi.org/10.1016/j.ijpddr.2017.11.005 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Sundaraneedi, Madhu Eichenberger, Ramon M. Al-Hallaf, Rafid Yang, Dai Sotillo, Javier Rajan, Siji Wangchuk, Phurpa Giacomin, Paul R. Keene, F. Richard Loukas, Alex Collins, J. Grant Pearson, Mark S. Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title | Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title_full | Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title_fullStr | Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title_full_unstemmed | Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title_short | Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
title_sort | polypyridylruthenium(ii) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724747/ https://www.ncbi.nlm.nih.gov/pubmed/29207309 http://dx.doi.org/10.1016/j.ijpddr.2017.11.005 |
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