ArticleAntimicrobial agents and chemotherapy2013
Identification and evaluation of novel acetolactate synthase inhibitors as antifungal agents.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
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- An Antifungal with a Novel Mechanism of Action Discovered via Resistance Gene-Guided Genome Mining.ACS central science · 2026Article
- Resistance Gene-Guided Discovery of a Fungal Spirotetramate as an Acetolactate Synthase Inhibitor.Journal of the American Chemical Society · 2025Article
- An easy and sensitive assay for acetohydroxyacid synthases based on the simultaneous detection of substrates and products in a single step.Analytical and bioanalytical chemistry · 2024Article
- The ilv2 gene, encoding acetolactate synthase for branched chain amino acid biosynthesis, is required for plant pathogenicity by Leptosphaeria maculans.Molecular biology reports · 2024Article
- Molecular Targets of Herbicides and Fungicides─Are There Useful Overlaps for Fungicide Discovery?Journal of agricultural and food chemistry · 2023Review
- Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry.Journal of medicinal chemistry · 2023Article
- Triazolopyrimidine herbicides are potent inhibitors of Aspergillus fumigatus acetohydroxyacid synthase and potential antifungal drug leads.Scientific reports · 2021Article
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- 5-methyl Furfural Reduces the Production of Malodors by Inhibiting Sodium l-lactate Fermentation ofMicroorganisms · 2019Article
- PHI-Nets: A Network Resource for Ascomycete Fungal Pathogens to Annotate and Identify Putative Virulence Interacting Proteins and siRNA Targets.Frontiers in microbiology · 2019Article
- Potential targets for the development of new antifungal drugs.The Journal of antibiotics · 2018Review
- Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Target Identification and Mechanism of Action of Picolinamide and Benzamide Chemotypes with Antifungal Properties.Cell chemical biology · 2018Article
- Structural insights into the mechanism of inhibition of AHAS by herbicides.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Rapid curation of gene disruption collections using Knockout Sudoku.Nature protocols · 2017Article
- High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.PLoS genetics · 2016Article
- Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease.PLoS pathogens · 2015Article
- Decatransin, a new natural product inhibiting protein translocation at the Sec61/SecYEG translocon.Journal of cell science · 2015Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-throughput phenotypic screening against the yeast Saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate the target of this series, we have applied a chemogenomic profiling approach using the S. cerevisiae deletion collection. All compounds of the series yielded highly similar profiles that suggested acetolactate synthase (Ilv2p, which catalyzes the first common step in branched-chain amino acid biosynthesis) as a possible target. The high correlation with profiles of known Ilv2p inhibitors like chlorimuron-ethyl provided further evidence for a similar mechanism of action. Genome-wide mutagenesis in S. cerevisiae identified 13 resistant clones with 3 different mutations in the catalytic subunit of acetolactate synthase that also conferred cross-resistance to established Ilv2p inhibitors. Mapping of the mutations into the published Ilv2p crystal structure outlined the chlorimuron-ethyl binding cavity, and it was possible to dock the triazolopyrimidine-sulfonamide compound into this pocket in silico. However, fungal growth inhibition could be bypassed through supplementation with exogenous branched-chain amino acids or by the addition of serum to the medium in all of the fungal organisms tested except for Aspergillus fumigatus. Thus, these data support the identification of the triazolopyrimidine-sulfonamide compounds as inhibitors of acetolactate synthase but suggest that targeting may be compromised due to the possibility of nutrient bypass in vivo.
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