ArticleACS infectious diseases2017
Combating Enhanced Intracellular Survival (Eis)-Mediated Kanamycin Resistance of Mycobacterium tuberculosis by Novel Pyrrolo[1,5-a]pyrazine-Based Eis Inhibitors.
Article in ACS infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Deferoxamine Exhibits Antimicrobial and Immunomodulatory Activity AgainstInternational journal of molecular sciences · 2026Article
- A small molecule inhibitor of RNA-binding protein IGF2BP3 shows anti-leukemic activity.Haematologica · 2026Article
- Design, Synthesis and Evaluation of Anticancer Potential of Novel Pyrrolopyrazines Against Glioblastoma: Mechanistic Details and In Vivo Safety Analysis.Archiv der Pharmazie · 2026Article
- Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.Molecular diversity · 2025Article
- Comparative Proteomic Analysis of Cell Wall Proteins of Aminoglycosides Resistant and SensitiveCurrent protein & peptide science · 2025Article
- Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin.The protein journal · 2024Article
- Synthesis and Biological Evaluation of 12-Aryl-11-hydroxy-5,6-dihydropyrrolo[2″,1″:3',4']pyrazino[1',2':1,5]pyrrolo[2,3-ACS omega · 2023Article
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Discovery and Mechanistic Analysis of Structurally Diverse Inhibitors of Acetyltransferase Eis among FDA-Approved Drugs.Biochemistry · 2023Article
- Discovery and development of inhibitors of acetyltransferase Eis to combat Mycobacterium tuberculosis.Methods in enzymology · 2023Article
- The role ofFrontiers in cellular and infection microbiology · 2023Review
- Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity.European journal of medicinal chemistry · 2022Article
- Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis fromRSC medicinal chemistry · 2021Article
- Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis fromACS chemical biology · 2020Article
- Comprehensive analysis of protein acetyltransferases of human pathogen Mycobacterium tuberculosis.Bioscience reports · 2019Article
- Probing the Robustness of Inhibitors of Tuberculosis Aminoglycoside Resistance Enzyme Eis by Mutagenesis.ACS infectious diseases · 2019Article
- Mycobacterial Aminoglycoside Acetyltransferases: A Little of Drug Resistance, and a Lot of Other Roles.Frontiers in microbiology · 2019Article
- Potent 1,2,4-Triazino[5,6 b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis.ACS infectious diseases · 2018Article
- Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities.Chemical Society reviews · 2018Review
- Acetylation by Eis and Deacetylation by Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and Structural Insight.Biochemistry · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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Abstract
Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Hence, the identification of highly effective antitubercular drugs with novel modes of action is crucial. In this paper, we report the discovery and development of pyrrolo[1,5-a]pyrazine-based analogues as highly potent inhibitors of the Mycobacterium tuberculosis (Mtb) acetyltransferase enhanced intracellular survival (Eis), whose up-regulation causes clinically observed resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN). We performed a structure-activity relationship (SAR) study to optimize these compounds as potent Eis inhibitors both against purified enzyme and in mycobacterial cells. A crystal structure of Eis in complex with one of the most potent inhibitors reveals that the compound is bound to Eis in the AG binding pocket, serving as the structural basis for the SAR. These Eis inhibitors have no observed cytotoxicity to mammalian cells and are promising leads for the development of innovative AG adjuvant therapies against drug-resistant TB.
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Registered trials
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