ArticleACS medicinal chemistry letters2011
CoA Adducts of 4-Oxo-4-Phenylbut-2-enoates: Inhibitors of MenB from the M. tuberculosis Menaquinone Biosynthesis Pathway.
Article in ACS medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Allosteric inhibition ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.BioMed research international · 2022Review
- Microwave-assisted synthesis of 4-oxo-2-butenoic acids by aldol-condensation of glyoxylic acid.RSC advances · 2021Article
- Endogenous Enzymes Enable Antimicrobial Activity.ACS chemical biology · 2021Article
- Bioenergetic Inhibitors: Antibiotic Efficacy and Mechanisms of Action inFrontiers in cellular and infection microbiology · 2020Review
- Novel MenA Inhibitors Are Bactericidal againstAntimicrobial agents and chemotherapy · 2019Article
- Structure-Based Design, Synthesis, and Biological Evaluation of Non-Acyl Sulfamate Inhibitors of the Adenylate-Forming Enzyme MenE.Biochemistry · 2019Article
- Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery.Pathogens (Basel, Switzerland) · 2018Review
- Generating enzyme and radical-mediated bisubstrates as tools for investigating Gcn5-related N-acetyltransferases.FEBS letters · 2017Article
- Novel long-chain compounds with both immunomodulatory and MenA inhibitory activities against Staphylococcus aureus and its biofilm.Scientific reports · 2017Article
- Stereoselective Synthesis, Docking, and Biological Evaluation of Difluoroindanediol-Based MenE Inhibitors as Antibiotics.Organic letters · 2016Article
- A Methyl 4-Oxo-4-phenylbut-2-enoate withACS infectious diseases · 2016Article
- Discovery of bicyclic inhibitors against menaquinone biosynthesis.Future medicinal chemistry · 2016Article
- Mechanism of MenE inhibition by acyl-adenylate analogues and discovery of novel antibacterial agents.Biochemistry · 2015Article
- Partial Saturation of Menaquinone inACS central science · 2015Article
- The tuberculosis drug discovery and development pipeline and emerging drug targets.Cold Spring Harbor perspectives in medicine · 2015Review
- The mycobacterial cell envelope-lipids.Cold Spring Harbor perspectives in medicine · 2014Review
- Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines.Molecular diversity · 2014Article
- New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.Journal of cheminformatics · 2014Article
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Authors and funding
9 authors.
Funding
Abstract
A high-throughput screen led to the discovery of 2-amino-4-oxo-4-phenylbutanoate inhibitors of the 1,4-dihydroxy-2-naphthoyl-CoA synthase (MenB) from the menaquinone biosynthesis pathway in Mycobacterium tuberculosis. However, these compounds are unstable in solution and eliminate to form the corresponding 4-oxo-4-phenylbut-2-enoates that then react with CoA in situ to form nanomolar inhibitors of MenB. The potency of these compounds results from interaction of the CoA adduct carboxylate with the MenB oxyanion hole, a conserved structural motif in the crotonase superfamily. 4-Oxo-4-chlorophenylbutenoyl methyl ester has MICs of 0.6 and 1.5 μg/ml against replicating and nonreplicating M. tuberculosis, respectively, and it is proposed that the methyl ester penetrates the cell where it is hydrolyzed and reacts with CoA to generate the active antibacterial. The CoA adducts thus represent an important foundation for the development of novel MenB inhibitors, and suggest a general approach to the development of potent inhibitors of acyl-CoA binding enzymes.
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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.