ArticleACS infectious diseases2018
Effects of the 1- N-(4-Amino-2 S-hydroxybutyryl) and 6'- N-(2-Hydroxyethyl) Substituents on Ribosomal Selectivity, Cochleotoxicity, and Antibacterial Activity in the Sisomicin Class of Aminoglycoside Antibiotics.
Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Plazomicin: A promising novel antimicrobial in the era of bacterial resistance (Review).Experimental and therapeutic medicine · 2026Review
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- Decarboxylation in Natural Products Biosynthesis.JACS Au · 2024Review
- Facile and selectiveGreen chemistry : an international journal and green chemistry resource : GC · 2022Article
- Synthesis and Antibacterial Activity of Propylamycin Derivatives Functionalized at the 5''- and Other Positions with a View to Overcoming Resistance Due to Aminoglycoside Modifying Enzymes.ACS infectious diseases · 2021Article
- Structural basis for plazomicin antibiotic action and resistance.Communications biology · 2021Article
- Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes.Scientific reports · 2021Article
- An Advanced Apralog with Increased in vitro and in vivo Activity toward Gram-negative Pathogens and Reduced ex vivo Cochleotoxicity.ChemMedChem · 2021Article
- Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells.Antibiotics (Basel, Switzerland) · 2020Article
- Apralogs: Apramycin 5-Journal of the American Chemical Society · 2020Article
- Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition.The Journal of biological chemistry · 2019Article
- Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.ACS infectious diseases · 2019Article
- Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives.MedChemComm · 2019Article
- Synthesis of saccharocin from apramycin and evaluation of its ribosomal selectivity.MedChemComm · 2019Article
- Design, Multigram Synthesis, and in Vitro and in Vivo Evaluation of Propylamycin: A Semisynthetic 4,5-Deoxystreptamine Class Aminoglycoside for the Treatment of Drug-Resistant Enterobacteriaceae and Other Gram-Negative Pathogens.Journal of the American Chemical Society · 2019Article
- Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation.EcoSal Plus · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Syntheses of the 6'- N-(2-hydroxyethyl) and 1- N-(4-amino-2 S-hydroxybutyryl) derivatives of the 4,6-aminoglycoside sisomicin and that of the doubly modified 1- N-(4-amino-2 S-hydroxybutyryl)-6'- N-(2-hydroxyethyl) derivative known as plazomicin are reported together with their antibacterial and antiribosomal activities and selectivities. The 6'- N-(2-hydroxyethyl) modification results in a moderate increase in prokaryotic/eukaryotic ribosomal selectivity, whereas the 1- N-(4-amino-2 S-hydroxybutyryl) modification has the opposite effect. When combined in plazomicin, the effects of the two groups on ribosomal selectivity cancel each other out, leading to the prediction that plazomicin will exhibit ototoxicity comparable to those of the parent and the current clinical aminoglycoside antibiotics gentamicin and tobramycin, as borne out by ex vivo studies with mouse cochlear explants. The 6'- N-(2-hydroxyethyl) modification restores antibacterial activity in the presence of the AAC(6') aminoglycoside-modifying enzymes, while the 1- N-(4-amino-2 S-hydroxybutyryl) modification overcomes resistance to the AAC(2') class but is still affected to some extent by the AAC(3) class. Neither modification is able to circumvent the ArmA ribosomal methyltransferase-induced aminoglycoside resistance. The use of phenyltriazenyl protection for the secondary amino group of sisomicin facilitates the synthesis of each derivative and their characterization through the provision of sharp NMR spectra for all intermediates.
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.