ArticleJournal of medicinal chemistry2018
Expanding Benzoxazole-Based Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure-Activity As Potential Antituberculosis Agents.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Substrate cooperativity shapes competitive inhibitor responses in mycobacterial inosine 5'-monophosphate dehydrogenase.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Deciphering the allosteric regulation of mycobacterial inosine-5'-monophosphate dehydrogenase.Nature communications · 2024Article
- The mycobacterial guaB1 gene encodes a guanosine 5'-monophosphate reductase with a cystathionine-β-synthase domain.The FEBS journal · 2022Article
- A d-Phenylalanine-Benzoxazole Derivative Reveals the Role of the Essential Enzyme Rv3603c in the Pantothenate Biosynthetic Pathway ofACS infectious diseases · 2022Article
- The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target forACS infectious diseases · 2021Article
- Enantioselective synthesis of chiral porphyrin macrocyclic hosts and kinetic enantiorecognition of viologen guests.Chemical science · 2021Article
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- Evaluation of Bronopol and Disulfiram as PotentialMolecules (Basel, Switzerland) · 2020Article
- Targeting Genome Integrity inMolecules (Basel, Switzerland) · 2020Review
- Structural characterization of glycinamide-RNase-transformylase T fromEmerging microbes & infections · 2020Article
- 2-Pyrazol-1-yl-thiazole derivatives as novel highly potent antibacterials.The Journal of antibiotics · 2019Article
- Drug-resistance inMedChemComm · 2019Review
- Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen.MedChemComm · 2019Article
- Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents.MedChemComm · 2019Review
- Synthesis and Structure-Activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH.European journal of medicinal chemistry · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis ( Mtb) inosine 5'-monophosphate dehydrogenase 2 ( MtbIMPDH2) is a promising yet controversial potential target. The inhibition of MtbIMPDH2 blocks the biosynthesis of guanine nucleotides, but high concentrations of guanine can potentially rescue the bacteria. Herein we describe an expansion of the structure-activity relationship (SAR) for the benzoxazole series of MtbIMPDH2 inhibitors and demonstrate that minimum inhibitory concentrations (MIC) of ≤1 μM can be achieved. The antibacterial activity of the most promising compound, 17b (Q151), is derived from the inhibition of MtbIMPDH2 as demonstrated by conditional knockdown and resistant strains. Importantly, guanine does not change the MIC of 17b, alleviating the concern that guanine salvage can protect Mtb in vivo. These findings suggest that MtbIMPDH2 is a vulnerable target for tuberculosis.
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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.