Identification of P218 as a Potent Inhibitor of Mycobacteria Ulcerans DHFR
| Autor: | Gustavo Pelicioli Riboldi, Rafael M. Couñago, Rachael Zigweid, Bart L. Staker, Stephen J. Mayclin, Peter J. Myler |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Buruli ulcer medicine.drug_class Drug discovery Antibiotics Biology Antimicrobial biology.organism_classification medicine.disease Microbiology chemistry.chemical_compound Enzyme chemistry Mycobacterium ulcerans Dihydrofolate reductase Antifolate parasitic diseases medicine biology.protein |
| DOI: | 10.26434/chemrxiv.12899420 |
| Popis: | Mycobacterium ulcerans is the causative agent of Buruli ulcer, a debilitating chronic disease that mainly affects the skin. Current treatments for Buruli ulcer are efficacious, but rely on the use of antibiotics with severe side effects. The enzyme dihydrofolate reductase (DHFR) plays a critical role in the de novo biosynthesis of folate species and is a validated target for several antimicrobials. Here we describe the biochemical and structural characterization of M. ulcerans DHFR and identified P218, a safe antifolate compound in clinical evaluation for malaria, as a potent inhibitor of this enzyme. We expect our results to advance M. ulcerans DHFR as a target for future structure-based drug discovery campaigns. |
| Databáze: | OpenAIRE |
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