ArticleEukaryotic cell2013
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.
Article in Eukaryotic cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 89 citations in OpenAlex.
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- New approaches for cryptococcosis treatment and prevention-a systematic review.Journal of thoracic disease · 2026Review
- Investigating the therapeutic potential of the antibacterial drug nitroxoline in combating cryptococcal infection.PLoS neglected tropical diseases · 2026Article
- A review of the current anti-New microbes and new infections · 2026Review
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- Antifungal Structure-Activity Relationship Studies of Broad-Spectrum Phenothiazines.ACS omega · 2025Article
- Accumulation of endogenous free radicals is required to induce titan-like cell formation inmBio · 2024Article
- Strategies of Pharmacological Repositioning for the Treatment of Medically Relevant Mycoses.Infection and drug resistance · 2024Review
- Proteasome inhibition as a therapeutic target for the fungal pathogenMicrobiology spectrum · 2023Article
- Recent drug development and treatments for fungal infections.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Review
- Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole.Journal of fungi (Basel, Switzerland) · 2023Article
- Development of an Imaging Flow Cytometry Method for Fungal Cytological Profiling and Its Potential Application in Antifungal Drug Development.Journal of fungi (Basel, Switzerland) · 2023Article
- Antifungal Development and the Urgency of Minimizing the Impact of Fungal Diseases on Public Health.ACS bio & med chem Au · 2023Review
- Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome.Molecules (Basel, Switzerland) · 2023Article
- Drug Target Elucidation Through Isolation and Analysis of Drug-Resistant Mutants in Cryptococcus neoformans.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A Dual-Readout High-Throughput Screening Assay for Small Molecules Active Against Aspergillus Fumigatus.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Small molecules for combating multidrug-resistant superbugActa pharmaceutica Sinica. B · 2022Review
- Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022Article
- Repurposing and optimization of drugs for discovery of novel antifungals.Drug discovery today · 2022Review
- Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum.Journal of industrial microbiology & biotechnology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
New, more accessible therapies for cryptococcosis represent an unmet clinical need of global importance. We took a repurposing approach to identify previously developed drugs with fungicidal activity toward Cryptococcus neoformans, using a high-throughput screening assay designed to detect drugs that directly kill fungi. From a set of 1,120 off-patent medications and bioactive molecules, we identified 31 drugs/molecules with fungicidal activity, including 15 drugs for which direct antifungal activity had not previously been reported. A significant portion of the drugs are orally bioavailable and cross the blood-brain barrier, features key to the development of a widely applicable anticryptococcal agent. Structural analysis of this set revealed a common chemotype consisting of a hydrophobic moiety linked to a basic amine, features that are common to drugs that cross the blood-brain barrier and access the phagolysosome, two important niches of C. neoformans. Consistent with their fungicidal activity, the set contains eight drugs that are either additive or synergistic in combination with fluconazole. Importantly, we identified two drugs, amiodarone and thioridazine, with activity against intraphagocytic C. neoformans. Finally, the set of drugs is also enriched for molecules that inhibit calmodulin, and we have confirmed that seven drugs directly bind C. neoformans calmodulin, providing a molecular target that may contribute to the mechanism of antifungal activity. Taken together, these studies provide a foundation for the optimization of the antifungal properties of a set of pharmacologically attractive scaffolds for the development of novel anticryptococcal therapies.
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