Niclosamide is active in vitro against mycetoma pathogens

Abdelhalim B. Mahmoud; Shereen Abd Algaffar; Wendy van de Sande; Sami Khalid; Marcel Kaiser; Pascal Mäser

doi:10.3390/molecules26134005

Niclosamide is active in vitro against mycetoma pathogens

Abdelhalim B. Mahmoud, Shereen Abd Algaffar, Wendy van de Sande, Sami Khalid, Marcel Kaiser, Pascal Mäser^*

^*Corresponding author for this work

Medical Microbiology & Infectious Diseases

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.

Original language	English
Article number	4005
Journal	Molecules
Volume	26
Issue number	13
DOIs	https://doi.org/10.3390/molecules26134005
Publication status	Published - 30 Jun 2021

Bibliographical note

Funding Information:
Funding: We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding Information:
We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank DNDi for the nitroheterocyclic drugs, Jonathan Vennerstrom for the peroxides, and Britta Lundstr?m-Stadelmann and Reto Rufener for MMV665807 and helpful advice. We are most grateful to Marcel Tanner and Suad Sulaiman for their continuous support.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Cite this

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title = "Niclosamide is active in vitro against mycetoma pathogens",

abstract = "Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.",

author = "Mahmoud, {Abdelhalim B.} and {Abd Algaffar}, Shereen and {van de Sande}, Wendy and Sami Khalid and Marcel Kaiser and Pascal M{\"a}ser",

note = "Funding Information: Funding: We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank DNDi for the nitroheterocyclic drugs, Jonathan Vennerstrom for the peroxides, and Britta Lundstr?m-Stadelmann and Reto Rufener for MMV665807 and helpful advice. We are most grateful to Marcel Tanner and Suad Sulaiman for their continuous support. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).",

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doi = "10.3390/molecules26134005",

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T1 - Niclosamide is active in vitro against mycetoma pathogens

AU - Mahmoud, Abdelhalim B.

AU - Abd Algaffar, Shereen

AU - van de Sande, Wendy

AU - Khalid, Sami

AU - Kaiser, Marcel

AU - Mäser, Pascal

N1 - Funding Information: Funding: We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We gratefully acknowledge financial support by the Emilia Guggenheim-Schnurr Foundation (www.ngib.ch/stiftung-egs/) to A.B.M. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank DNDi for the nitroheterocyclic drugs, Jonathan Vennerstrom for the peroxides, and Britta Lundstr?m-Stadelmann and Reto Rufener for MMV665807 and helpful advice. We are most grateful to Marcel Tanner and Suad Sulaiman for their continuous support. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

PY - 2021/6/30

Y1 - 2021/6/30

N2 - Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.

AB - Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.

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U2 - 10.3390/molecules26134005

DO - 10.3390/molecules26134005

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SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 13

M1 - 4005

ER -

Niclosamide is active in vitro against mycetoma pathogens

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