ArticleCell chemical biology2023
Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Compound Z247611722 Exhibits Antifungal Activity by Inhibiting Serine Palmitoyltransferase.Nature communications · 2026Article
- The novel antifungal agent NPD2560 perturbs the Rho1-centered signaling network to induce a cell wall integrity response.Microbiology spectrum · 2026Article
- The emerging pathogen Candida auris: host interactions and disease drivers.Journal of biomedical science · 2026Review
- Sterol-C4-methyl-oxidase Erg251 governs Candida albicans hypoxic growth, commensalism and virulence.Nature communications · 2025Article
- Antifungal Activities of Multi-Halogenated Indoles Against Drug-ResistantInternational journal of molecular sciences · 2025Article
- Target product profile and discovery and development path for novel cryptococcal disease treatments.The Journal of infection · 2025Review
- Coniontins, lipopetaibiotics active against Candida auris identified from a microbial natural product fractionation library.Nature communications · 2025Article
- Colistin enhances caspofungin antifungal efficacy against Aspergillus fumigatus by modulating calcium homeostasis and stress responses.Nature communications · 2025Article
- Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.npj antimicrobials and resistance · 2025Review
- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
- Novel Triazeneindole Antibiotics: Synthesis and Hit-to-Lead Optimization.International journal of molecular sciences · 2025Article
- Integration of Transcriptomics and Proteomics to Elucidate Inhibitory Effect and Mechanism of Antifungalmycin B from MarineMarine drugs · 2025Article
- Discovery of novel targets for important human and plant fungal pathogens via an automated computational pipeline HitList.PloS one · 2025Article
- Interdisciplinary approaches for the discovery of novel antifungals.Trends in molecular medicine · 2024Review
- Brilacidin, a novel antifungal agent againstmBio · 2024Article
- Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.Cell chemical biology · 2024Article
- Advancements and challenges in antifungal therapeutic development.Clinical microbiology reviews · 2024Review
- Article
- Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination.Antimicrobial agents and chemotherapy · 2024Article
- Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents againstFrontiers in cellular and infection microbiology · 2024Article
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 3 countries.
Funding
Abstract
Rising drug resistance among pathogenic fungi, paired with a limited antifungal arsenal, poses an increasing threat to human health. To identify antifungal compounds, we screened the RIKEN natural product depository against representative isolates of four major human fungal pathogens. This screen identified NPD6433, a triazenyl indole with broad-spectrum activity against all screening strains, as well as the filamentous mold Aspergillus fumigatus. Mechanistic studies indicated that NPD6433 targets the enoyl reductase domain of fatty acid synthase 1 (Fas1), covalently inhibiting its flavin mononucleotide-dependent NADPH-oxidation activity and arresting essential fatty acid biosynthesis. Robust Fas1 inhibition kills Candida albicans, while sublethal inhibition impairs diverse virulence traits. At well-tolerated exposures, NPD6433 extended the lifespan of nematodes infected with azole-resistant C. albicans. Overall, identification of NPD6433 provides a tool with which to explore lipid homeostasis as a therapeutic target in pathogenic fungi and reveals a mechanism by which Fas1 function can be inhibited.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.