Antibiotic resistance is rising at an alarming rate, yet new antimicrobial agents remain scarce. Natural products offer exceptional structural diversity and inherent bioactivity, but their clinical translation is hindered by poor stability, bioavailability, and efficacy. Increasingly, researchers are addressing these limitations by using natural compounds as antibacterial leads, synergistic components, and modifiable scaffolds for structural optimization and advanced delivery. This integrated approach defines the progress highlighted in this Research Topic.
The six contributions in this Research Topic illustrate how natural products continue to serve not only as a source of antimicrobial leads but also as a foundation for subsequent optimization (Table 1; Figure 1). Several studies reaffirmed the intrinsic antibacterial activity of plant- and bee-derived compounds. Murugesan et al. identified 2,4-di-tert-butylphenol from Clidemia hirta as an active agent against Pseudomonas aeruginosa, while Tao et al. demonstrated that carvacrol, a major constituent of oregano essential oil, exhibits broad-spectrum bactericidal activity. Similarly, Martins et al. reported the potent antimycobacterial activity of Brazilian red propolis extract, and Osei Duah et al. identified diverse plant-derived scaffolds as promising candidates for treating ocular tuberculosis. Together, these findings reinforce the continued relevance of natural sources in antimicrobial discovery.
TABLE 1
| Study | Natural agent | Partner drug/Agent | Target germ | Main mechanism |
|---|---|---|---|---|
| Osei Duah et al. | Safranal | Crocin, Crocetin | E. coli S. aureus | Multiple entry points into the germ |
| Tao et al. | Carvacrol | Tobramycin | MRSA, E. coli | Perforating the cell membrane |
| Li et al. | Pleuromutilin core | Pyrrole group | MRSA, MRSE | Blocking the PTC in the ribosome |
| Martins et al. | Red propolis | Biofilm, Macrophages | M. tuberculosis | Inhibiting biofilm and clearing intracellular bacilli |
| Murugesan et al. | Clidemia hirta | PBP2a protein | P. aeruginosa | Binding and inhibiting the cell wall protein |
Natural product-based antibacterial strategies and mechanisms.
FIGURE 1
Beyond their inherent antibacterial activity, these studies further highlight the critical role of combination strategies in enhancing antimicrobial efficacy. Tao et al. showed that carvacrol can potentiate tobramycin activity via disruption of bacterial membrane integrity, while Baraich et al. employed a simplex-centroid mixture design to reveal pronounced synergistic interactions among saffron-derived compounds. These observations reflect a broader shift toward leveraging synergistic combinations to amplify antibacterial performance and address resistance.
At the same time, translating natural compounds into clinically viable agents increasingly depends on structural refinement and advanced delivery strategies. Osei Duah et al. emphasized the role of nanocarriers, liposomal systems, and in situ gels in overcoming pharmacokinetic and physiological barriers, particularly in ocular applications. Complementing this, Li et al. developed a pleuromutilin derivative with potent activity against multidrug-resistant Gram-positive bacteria, demonstrating how targeted structural modification can improve efficacy, safety, and resistance profiles.
Taken together, the studies featured in this Research Topic highlight a clear transition from simple activity screening toward more integrated approaches that combine discovery, synergistic optimization, and rational design. These strategies will likely play a central role in advancing natural products from promising bioactive compounds to clinically relevant antimicrobial agents.
Looking ahead, continued progress in this field will rely on close integration across disciplines, including chemistry, microbiology, materials science, and pharmacology. Multidisciplinary collaboration will be essential to fully realize the therapeutic potential of natural products and to develop effective and safe antimicrobial agents capable of addressing the ongoing challenge of drug resistance.
Statements
Author contributions
SS: Funding acquisition, Project administration, Visualization, Writing – original draft, Writing – review and editing, Conceptualization, Software. RW: Software, Writing – original draft, Conceptualization, Visualization. LL: Software, Visualization, Writing – review and editing. YZ: Investigation, Writing – original draft, Software. LW: Software, Visualization, Writing – original draft. YW: Data curation, Investigation, Writing – review and editing, Conceptualization, Supervision, Visualization, Writing – original draft. YY: Writing – review and editing, Supervision, Conceptualization, Investigation, Methodology, Writing – original draft.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This study was supported in part by grants from the Shandong Provincial Natural Science Foundation (ZR2025QC153), the National Key Laboratory of Veterinary Public Health Safety (Z-2025SKLVPHS19), the Taishan Scholars Program (tsqn202408303), and the Agricultural Science and Technology Innovation Project of the Shandong Academy of Agricultural Sciences (CXGC 2026D12).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
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Summary
Keywords
antibacterial derivatives, drug resistance, natural products, structural modification, synergistic combination
Citation
Song S, Wei R, Li L, Zhang Y, Wang L, Wang Y and Yi Y (2026) Editorial: Design and synthesis of natural antibacterial derivatives. Front. Pharmacol. 17:1837910. doi: 10.3389/fphar.2026.1837910
Received
24 March 2026
Revised
08 April 2026
Accepted
13 April 2026
Published
23 April 2026
Volume
17 - 2026
Edited and reviewed by
Hendrik W. Van Veen, University of Cambridge, United Kingdom
Updates
Copyright
© 2026 Song, Wei, Li, Zhang, Wang, Wang and Yi.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yao Wang, wenshuowy@163.com; Yunpeng Yi, yiyp@foxmail.com
† These authors have contributed equally to this work
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.