ArticleJournal of medicinal chemistry2016
Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery.Molecular diversity · 2025Article
- Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin.The protein journal · 2024Article
- 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
- 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
- Synthesis and Biological Evaluation of Novel Benzhydrylpiperazine-Coupled Nitrobenzenesulfonamide Hybrids.ACS omega · 2021Article
- Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis fromACS chemical biology · 2020Article
- 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
- Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries.International journal of antimicrobial agents · 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
- Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors.Molecules (Basel, Switzerland) · 2018Review
- Interfering With DNA Decondensation as a Strategy Against Mycobacteria.Frontiers in microbiology · 2018Article
- The Role of Antibiotic-Target-Modifying and Antibiotic-Modifying Enzymes inFrontiers in microbiology · 2018Review
- Amikacin: Uses, Resistance, and Prospects for Inhibition.Molecules (Basel, Switzerland) · 2017Review
- Combating Enhanced Intracellular Survival (Eis)-Mediated Kanamycin Resistance of Mycobacterium tuberculosis by Novel Pyrrolo[1,5-a]pyrazine-Based Eis Inhibitors.ACS infectious diseases · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28-37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.
Indexed as
Identifiers
What OpenQuestion holds
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.