Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an Open Source Drug discovery approach

Lim, Wilson; Verbon, Annelies; Sande, Wendy W. J. van de

doi:10.1080/17460441.2022.2080195

Cited by 12 publications

(10 citation statements)

References 161 publications

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“…At this time approximately 2,100 compounds have been screened for their activity against M. mycetomatis in vitro ; 1,600 originating from the Medicines for Malaria Venture (MMV) open boxes, and 510 donated or generated by the MycetOS community itself ( Lim et al, 2018 ; Lim et al, 2022a ; Lim et al, 2022b ; OpenSourceMycetoma, 2023 ). From those 1,600 compounds screened, 404 inhibited M. mycetomatis growth at a concentration of 100 μM and 26 had an IC50 < 8 µM.…”

Section: Novel Antifungal Agents and Approaches To Treatmentmentioning

confidence: 99%

An update on the development of novel antifungal agents for eumycetoma

2023

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Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation of the affected limb. More effective treatments are needed for eumycetoma. This article will describe some of the approaches being used to develop and evaluate new treatments for eumycetoma, summarise the latest developments and discuss the challenges that lie ahead.

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Section: Novel Antifungal Agents and Approaches To Treatmentmentioning

confidence: 99%

An update on the development of novel antifungal agents for eumycetoma

2023

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“…The screening of chemical boxes from the Medicines for Malaria Venture (MMV, Geneva, Switzerland) led to the identification of fenarimols as promising drug candidates for the treatment of M. mycetomatis [5] . This development culminated in the establishment of an open science research network for the discovery of new eumycetoma drugs (MycetOS), which has identified further promising compound classes such as benzimidazoles, thiazoles, and melanin inhibitors, in addition to fenarimols [6,7] …”

Section: Introductionmentioning

confidence: 99%

“…[5] This development culminated in the establishment of an open science research network for the discovery of new eumycetoma drugs (MycetOS), which has identified further promising compound classes such as benzimidazoles, thiazoles, and melanin inhibitors, in addition to fenarimols. [6,7] Melanin biosynthesis is a vital factor for M. mycetomatis, which forms black grains during its development in the host, and melanin protects the fungus from stress factors and antifungal azole drugs. [8] Combination of melanin inhibitors with itraconazole showed promising in vivo therapeutic effects in M. mycetomatis-infected Galleria mellonella larvae.…”

Section: Introductionmentioning

confidence: 99%

Antifungal Activity of Natural Naphthoquinones and Anthraquinones against Madurella mycetomatis

Todd

Sande

et al. 2023

Chemistry & Biodiversity

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Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal drugs. In this study, a series of natural naphthoquinones and anthraquinones was evaluated for their activity against Madurella mycetomatis, which is the most common causative agent of eumycetoma. The metabolic activity of Madurella mycetomatis as well as the viability of Galleria mellonella larvae upon treatment with quinones was investigated. Several hydroxy‐substituted naphthoquinones exhibited activity against Madurella mycetomatis. In particular, naphthazarin (5,8‐dihydroxy‐1,4‐naphthoquinone) was identified as a considerably active antifungal compound against Madurella mycetomatis (IC50=1.4 μM), while it showed reduced toxicity to Galleria mellonella larvae, which is a well‐established in vivo invertebrate model for mycetoma drug studies.

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“…Among the actions identified in the road map, several related to the development of point-of-care diagnostic tests to improve diagnostic capacity, as well as availability of treatment regimens with improved efficacy, and design of shorter and higher efficacy regimens for mycetoma and chromoblastomycosis. Treatment efficacy with itraconazole is reported to be very low for eumycetoma (<30%) [ 5 , 6 ]. This survey further contributes to the understanding of treatment and programmatic challenges for this group of diseases.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic capacities and treatment practices on implantation mycoses: Results from the 2022 WHO global online survey

et al. 2023

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Between January and March 2022, WHO conducted a global online survey to collect data on diagnostic capacities and treatment practices in different settings for four implantation mycoses: eumycetoma, actinomycetoma, cutaneous sporotrichosis and chromoblastomycosis. The survey investigated the type of diagnostic methods available in countries at various health system levels (tertiary, secondary, primary level) and the medicines used to treat implantation mycoses, with a view to understanding the level of drug repurposing for treatment of these diseases. 142 respondents from 47 countries, including all continents, contributed data: 60% were from middle-income countries, with 59% working at the tertiary level of the health system and 30% at the secondary level. The results presented in this article provide information on the current diagnostic capacity and treatment trends for both pharmacological and non-pharmacological interventions. In addition, the survey provides insight on refractory case rates, as well as other challenges, such as availability and affordability of medicines, especially in middle-income countries. Although the study has limitations, the survey-collected data confirms that drug repurposing is occurring for all four surveyed implantation mycoses. The implementation of an openly accessible global and/or a national treatment registry for implantation mycoses could contribute to address the gaps in epidemiological information and collect valuable observational data to inform treatment guidelines and clinical research.

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Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an Open Source Drug discovery approach

Cited by 12 publications

References 161 publications

An update on the development of novel antifungal agents for eumycetoma

An update on the development of novel antifungal agents for eumycetoma

Antifungal Activity of Natural Naphthoquinones and Anthraquinones against Madurella mycetomatis

Diagnostic capacities and treatment practices on implantation mycoses: Results from the 2022 WHO global online survey

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