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

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
13 Downloads (Pure)

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 languageEnglish
Article number4005
JournalMolecules
Volume26
Issue number13
DOIs
Publication statusPublished - 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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