---
title: "Neomycin-oxazolidinone hybrid antibiotics potentiate activity against Pseudomonas aeruginosa via o"
id: "pubmed-42526133"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42526133"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42526133/"
doi: "10.1016/j.bioorg.2026.110287"
published_at: "2026-10-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neomycin-oxazolidinone hybrid antibiotics potentiate activity against Pseudomonas aeruginosa via o
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42526133
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42526133/)
- **DOI:** [10.1016/j.bioorg.2026.110287](https://doi.org/10.1016%2Fj.bioorg.2026.110287)
- **Published At:** 2026-10-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Antibiotic resistance among multidrug-resistant pathogens motivates alternative antibacterial strategies beyond conventional bactericidal agents. The study reports design and synthesis of 14 hybrid antibiotics combining **neomycin** and oxazolidinone cores. - The library included one direct neomycin-tedizolid hybrid, nine tedizolid–neomycin hybrids with varying alkyl linker lengths, and four linezolid–neomycin hybrids with different linker lengths. - Antibacterial spectrum screening across ESKAPEE pathogens identified compound **H08** as a representative hybrid with activity against S. aureus and E. coli comparable to the parent antibiotics. - Structure–activity relationship analysis indicated that **linker length** clearly influenced antibacterial activity among the hybrids. - H08 showed **synergistic antibacterial activity** with all eight clinically used antibiotics tested against **Pseudomonas aeruginosa**, with the strongest synergy observed with **novobiocin**, whose MIC decreased 128-fold when combined with H08. - Mechanistic experiments attributed the synergistic effects primarily to **outer membrane disruption**, which enhanced intracellular accumulation of co-administered antibiotics. - Representative hybrids, including H08, displayed low cytotoxicity toward mammalian cells in the assays reported. - The authors propose **neomycin-oxazolidinone hybrids** as promising antibiotic adjuvants to potentiate existing antibiotics against Gram-negative pathogens and as a strategy to address multidrug-resistant bacterial infections. - Keywords reported: **Antibiotic synergy; Antimicrobial resistance; Hybrid antibiotics; Neomycin; Oxazolidinone.**
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 28. # Design and synthesis of neomycin-oxazolidinone hybrid antibiotics: exhibiting synergistic activity against Pseudomonas aeruginosa via outer membrane disruption [Yinzhe Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42526133)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-1 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Weiding Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+W&cauthor_id=42526133)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-1 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Wenbo Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+W&cauthor_id=42526133)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-2 "Institute of Science Tokyo, Department of Life Science, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan."), [Xia Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+X&cauthor_id=42526133)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-3 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China."), [Hongke Hao](https://pubmed.ncbi.nlm.nih.gov/?term=Hao+H&cauthor_id=42526133)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-3 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China."), [Lifeng Ding](https://pubmed.ncbi.nlm.nih.gov/?term=Ding+L&cauthor_id=42526133)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-4 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China."), [Ishwar Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+I&cauthor_id=42526133)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-5 "Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Yongtao Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+Y&cauthor_id=42526133)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-6 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: Yongtao.Zhu@xjtlu.edu.cn."), [Qian Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Q&cauthor_id=42526133)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#full-view-affiliation-7 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. Electronic address: qian.zhang02@xjtlu.edu.cn.") Affiliations Expand ### Affiliations * 1 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK. * 2 Institute of Science Tokyo, Department of Life Science, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan. * 3 Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. * 4 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. * 5 Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK. * 6 Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: Yongtao.Zhu@xjtlu.edu.cn. * 7 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. Electronic address: qian.zhang02@xjtlu.edu.cn. * PMID: **42526133** * DOI: [ 10.1016/j.bioorg.2026.110287 ](https://doi.org/10.1016/j.bioorg.2026.110287) Item in Clipboard # Design and synthesis of neomycin-oxazolidinone hybrid antibiotics: exhibiting synergistic activity against Pseudomonas aeruginosa via outer membrane disruption Yinzhe Chen et al. Bioorg Chem. 2026. Show details Display options Display options Format Abstract PubMed PMID Bioorg Chem Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Bioorg+Chem%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Bioorg+Chem%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42526133/) . 2026 Oct 5:181:110287. doi: 10.1016/j.bioorg.2026.110287. Epub 2026 Jul 28. ### Authors [Yinzhe Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42526133)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-1 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Weiding Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+W&cauthor_id=42526133)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-1 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Wenbo Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+W&cauthor_id=42526133)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-2 "Institute of Science Tokyo, Department of Life Science, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan."), [Xia Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+X&cauthor_id=42526133)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-3 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China."), [Hongke Hao](https://pubmed.ncbi.nlm.nih.gov/?term=Hao+H&cauthor_id=42526133)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-3 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China."), [Lifeng Ding](https://pubmed.ncbi.nlm.nih.gov/?term=Ding+L&cauthor_id=42526133)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-4 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China."), [Ishwar Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+I&cauthor_id=42526133)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-5 "Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK."), [Yongtao Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+Y&cauthor_id=42526133)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-6 "Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: Yongtao.Zhu@xjtlu.edu.cn."), [Qian Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Q&cauthor_id=42526133)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42526133/#short-view-affiliation-7 "Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. Electronic address: qian.zhang02@xjtlu.edu.cn.") ### Affiliations * 1 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK. * 2 Institute of Science Tokyo, Department of Life Science, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8550, Japan. * 3 Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. * 4 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. * 5 Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK. * 6 Department of Biosciences and Bioinformatics, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: Yongtao.Zhu@xjtlu.edu.cn. * 7 Department of Chemistry and Materials Science, Xi'an-Jiaotong Liverpool University, Suzhou, Jiangsu Province, 215123, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK; Advanced Materials Research Center, School of Science, Xi'an-Jiaotong Liverpool University, Suzhou 215123, PR China. Electronic address: qian.zhang02@xjtlu.edu.cn. * PMID: **42526133** * DOI: [ 10.1016/j.bioorg.2026.110287 ](https://doi.org/10.1016/j.bioorg.2026.110287) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Antibiotic resistance among multidrug-resistant pathogens has become a major global health challenge, highlighting the urgent need for new antibacterial strategies beyond conventional bactericidal agents. In this study, we designed and synthesized 14 neomycin-oxazolidinone hybrid antibiotics, comprising one direct neomycin-tedizolid hybrid, nine tedizolid-neomycin hybrids with alkyl linkers of varying lengths, and four linezolid-neomycin hybrids with different linker lengths. Following antibacterial spectrum evaluation against ESKAPEE pathogens, the representative compound H08 exhibited antibacterial activity against S. aureus and E. coli comparable to that of the parent antibiotics. Structure-activity relationship analysis revealed a clear influence of linker length on antibacterial activity. More importantly, H08 demonstrated synergistic antibacterial activity with all eight clinically used antibiotics evaluated against P. aeruginosa. Notably, the strongest synergistic effect was observed with novobiocin, whose MIC was reduced by 128-fold in the presence of H08. Mechanistic studies demonstrated that this synergistic effect primarily resulted from disruption of the bacterial outer membrane, thereby facilitating intracellular accumulation of co-administered antibiotics. In addition, the representative hybrids exhibited low cytotoxicity toward mammalian cells. These findings identify neomycin-oxazolidinone hybrids as promising antibiotic adjuvants for potentiating the activity of existing antibiotics against Gram-negative pathogens and provide a useful strategy for combating multidrug-resistant bacterial infections. **Keywords:** Antibiotic synergy; Antimicrobial resistance; Hybrid antibiotics; Neomycin; Oxazolidinone. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Design, synthesis and antibacterial evaluation of novel unsaturated butenolide-fatty amine hybrids against multidrug-resistant pathogens. ](https://pubmed.ncbi.nlm.nih.gov/42167554/) Tang SY, Wang YP, Qin DM, Zhang XM, Liu XJ, Zi XQ, Zhu SY, Pu H, Zhao Q.Tang SY, et al.Bioorg Med Chem Lett. 2026 Sep;138:130690. doi: 10.1016/j.bmcl.2026.130690. Epub 2026 May 20.Bioorg Med Chem Lett. 2026.PMID: 42167554 * [ Design SMAP29-LysPA26 as a Highly Efficient Artilysin against Pseudomonas aeruginosa with Bactericidal and Antibiofilm Activity. ](https://pubmed.ncbi.nlm.nih.gov/34878337/) Wang T, Zheng Y, Dai J, Zhou J, Yu
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