In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis.
Background Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug...
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ftdoajarticles:oai:doaj.org/article:7166623fbb284ea9ab8a43b71e61bb6f 2023-05-15T15:09:39+02:00 In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. Supriya Khanra Subir Kumar Juin Junaid Jibran Jawed Sweta Ghosh Shreyasi Dutta Shaik Abdul Nabi Jyotirmayee Dash Dipak Dasgupta Subrata Majumdar Rahul Banerjee 2020-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008575 https://doaj.org/article/7166623fbb284ea9ab8a43b71e61bb6f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008575 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008575 https://doaj.org/article/7166623fbb284ea9ab8a43b71e61bb6f PLoS Neglected Tropical Diseases, Vol 14, Iss 8, p e0008575 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008575 2022-12-31T13:48:05Z Background Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/principal Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/significance All experiments affirmed the efficacy of suramin against L. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 8 e0008575 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Supriya Khanra Subir Kumar Juin Junaid Jibran Jawed Sweta Ghosh Shreyasi Dutta Shaik Abdul Nabi Jyotirmayee Dash Dipak Dasgupta Subrata Majumdar Rahul Banerjee In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/principal Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/significance All experiments affirmed the efficacy of suramin against L. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL. |
format |
Article in Journal/Newspaper |
author |
Supriya Khanra Subir Kumar Juin Junaid Jibran Jawed Sweta Ghosh Shreyasi Dutta Shaik Abdul Nabi Jyotirmayee Dash Dipak Dasgupta Subrata Majumdar Rahul Banerjee |
author_facet |
Supriya Khanra Subir Kumar Juin Junaid Jibran Jawed Sweta Ghosh Shreyasi Dutta Shaik Abdul Nabi Jyotirmayee Dash Dipak Dasgupta Subrata Majumdar Rahul Banerjee |
author_sort |
Supriya Khanra |
title |
In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
title_short |
In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
title_full |
In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
title_fullStr |
In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
title_full_unstemmed |
In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
title_sort |
in vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008575 https://doaj.org/article/7166623fbb284ea9ab8a43b71e61bb6f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 8, p e0008575 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008575 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008575 https://doaj.org/article/7166623fbb284ea9ab8a43b71e61bb6f |
op_doi |
https://doi.org/10.1371/journal.pntd.0008575 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
8 |
container_start_page |
e0008575 |
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1766340798620631040 |