ArticlePloS one2011
New classes of alanine racemase inhibitors identified by high-throughput screening show antimicrobial activity against Mycobacterium tuberculosis.
Article in PloS one, 2011. 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, 53 citations in OpenAlex.
- Deep learning-enabled discovery of antibiotics effective againstScience translational medicine · 2026Article
- D-alanine aminotransferase (Dat) promotesbioRxiv : the preprint server for biology · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Low-cost anti-mycobacterial drug discovery using engineered E. coli.Nature communications · 2022Article
- Purification, Characterization and Inhibition of Alanine Racemase from a Pathogenic Strain ofPolish journal of microbiology · 2019Article
- Knockout of alanine racemase gene attenuates the pathogenicity of Aeromonas hydrophila.BMC microbiology · 2019Article
- A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis.PloS one · 2019Article
- A Standard Method To Inactivate Bacillus anthracis Spores to Sterility via Gamma Irradiation.Applied and environmental microbiology · 2018Article
- Identification of a new alanine racemase inGut pathogens · 2018Article
- Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.Antimicrobial agents and chemotherapy · 2017Article
- Selection and characterization of alanine racemase inhibitors against Aeromonas hydrophila.BMC microbiology · 2017Article
- Probing the Catalytic Charge-Relay System in Alanine Racemase with Genetically Encoded Histidine Mimetics.ACS chemical biology · 2016Article
- Mechanistic and Evolutionary Insights from the Reciprocal Promiscuity of Two Pyridoxal Phosphate-dependent Enzymes.The Journal of biological chemistry · 2016Article
- The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan.Cold Spring Harbor perspectives in medicine · 2015Review
- High throughput screen identifies small molecule inhibitors specific for Mycobacterium tuberculosis phosphoserine phosphatase.The Journal of biological chemistry · 2014Article
- Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition.Antimicrobial agents and chemotherapy · 2014Article
- New 2-thiopyridines as potential candidates for killing both actively growing and dormant Mycobacterium tuberculosis cells.Antimicrobial agents and chemotherapy · 2014Article
- Inhibition of mycobacterial alanine racemase activity and growth by thiadiazolidinones.Biochemical pharmacology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn an effort to discover new drugs to treat tuberculosis (TB) we chose alanine racemase as the target of our drug discovery efforts. In Mycobacterium tuberculosis, the causative agent of TB, alanine racemase plays an essential role in cell wall synthesis as it racemizes L-alanine into D-alanine, a key building block in the biosynthesis of peptidoglycan. Good antimicrobial effects have been achieved by inhibition of this enzyme with suicide substrates, but the clinical utility of this class of inhibitors is limited due to their lack of target specificity and toxicity. Therefore, inhibitors that are not substrate analogs and that act through different mechanisms of enzyme inhibition are necessary for therapeutic development for this drug target. METHODOLOGY/PRINCIPAL
findingsTo obtain non-substrate alanine racemase inhibitors, we developed a high-throughput screening platform and screened 53,000 small molecule compounds for enzyme-specific inhibitors. We examined the 'hits' for structural novelty, antimicrobial activity against M. tuberculosis, general cellular cytotoxicity, and mechanism of enzyme inhibition. We identified seventeen novel non-substrate alanine racemase inhibitors that are structurally different than any currently known enzyme inhibitors. Seven of these are active against M. tuberculosis and minimally cytotoxic against mammalian cells. CONCLUSIONS/SIGNIFICANCE: This study highlights the feasibility of obtaining novel alanine racemase inhibitor lead compounds by high-throughput screening for development of new anti-TB agents.
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Registered trials
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