ArticlemBio2014
Identification and evaluation of improved 4'-O-(alkyl) 4,5-disubstituted 2-deoxystreptamines as next-generation aminoglycoside antibiotics.
Article in mBio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Synthesis of 4-Tetrahedron · 2023Article
- Synthesis, Antibacterial and Antiribosomal Activity of the 3Antibiotics (Basel, Switzerland) · 2022Article
- Structure-Activity Relationships for 5'' Modifications of 4,5-Aminoglycoside Antibiotics.ChemMedChem · 2022Article
- Influence of ring size in conformationally restricted ring I analogs of paromomycin on antiribosomal and antibacterial activity.RSC medicinal chemistry · 2021Article
- 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
- En Route to the Transformation of Glycoscience: A Chemist's Perspective on Internal and External Crossroads in Glycochemistry.Journal of the American Chemical Society · 2021Article
- Synthesis of a Pseudodisaccharide Suitable for Synthesis of Ring I Modified 4,5-2-Deoxystreptamine Type Aminoglycoside Antibiotics.The Journal of organic chemistry · 2020Article
- Stereospecific synthesis of methyl 2-amino-2,4-dideoxy-6S-deuterio-α-D-xylo-hexopyranoside and methyl 2-amino-2,4-dideoxy-6S-deuterio-4-propyl-α-d-glucopyranoside: Side chain conformation of the novel aminoglycoside antibiotic propylamycin.Carbohydrate research · 2020Article
- Apralogs: Apramycin 5-Journal of the American Chemical Society · 2020Article
- Use of a fluorescence assay to determine relative affinities of semisynthetic aminoglycosides to small RNAs representing bacterial and mitochondrial A sites.Bioorganic & medicinal 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
- Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design.Biomimetics (Basel, Switzerland) · 2019Review
- Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives.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
- Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use.Scientific reports · 2019Article
- Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation.EcoSal Plus · 2018Review
- Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.EMBO reports · 2018Article
- Evaluation of Aminoglycoside and Carbapenem Resistance in a Collection of Drug-Resistant Pseudomonas aeruginosa Clinical Isolates.Microbial drug resistance (Larchmont, N.Y.) · 2018Article
- 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.ACS infectious diseases · 2018Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledThe emerging epidemic of drug resistance places the development of efficacious and safe antibiotics in the spotlight of current research. Here, we report the design of next-generation aminoglycosides. Discovery efforts were driven by rational synthesis focusing on 4' alkylations of the aminoglycoside paromomycin, with the goal to alleviate the most severe and disabling side effect of aminoglycosides-irreversible hearing loss. Compounds were evaluated for target activity in in vitro ribosomal translation assays, antibacterial potency against selected pathogens, cytotoxicity against mammalian cells, and in vivo ototoxicity. The results of this study produced potent compounds with excellent selectivity at the ribosomal target, promising antibacterial activity, and little, if any, ototoxicity upon chronic administration. The favorable biocompatibility profile combined with the promising antibacterial activity emphasizes the potential of next-generation aminoglycosides in the treatment of infectious diseases without the risk of ototoxicity. IMPORTANCE: The ever-widening epidemic of multidrug-resistant infectious diseases and the paucity of novel antibacterial agents emerging from modern screening platforms mandate the reinvestigation of established drugs with an emphasis on improved biocompatibility and overcoming resistance mechanisms. Here, we describe the preparation and evaluation of derivatives of the established aminoglycoside antibiotic paromomycin that effectively remove its biggest deficiency, ototoxicity, and overcome certain bacterial resistance mechanisms.
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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.