Henry, Samantha A., Sansom, Geraud N., Tran, Thao Thi Phuong, Boughton, Ryan A., Joiner, Guy, Webster, Calum M., de Silva, H. Ireshika C., Garrett, Michelle D., Serpell, Christopher J., Robinson, Gary K., and others. (2026) Investigating the role of cytochrome bd oxidases in the antibacterial activity of madecassic acid and derivatives thereof. RSC Medicinal Chemistry, . E-ISSN 2632-8682. (doi:10.1039/d5md01116g) (KAR id:112819)
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Language: English 
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| Official URL: https://doi.org/10.1039/d5md01116g |
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| Resource title: | Investigating the role of cytochrome bd oxidases in the antibacterial activity of madecassic acid and derivatives thereof |
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| Resource type: | Pre-print |
| DOI: | 10.26434/chemrxiv-2025-6wj5j |
| KDR/KAR URL: | https://kar.kent.ac.uk/112389/ |
| External URL: | https://doi.org/10.26434/chemrxiv-2025-6wj5j |
Abstract
Natural products are valuable starting points for drug discovery, although individual modes of action are often difficult to pin down. Ursanes such as madecassic acid have been shown to have antibacterial properties, but a variety of mechanisms have been proposed. In this paper, we report previously uninvestigated activity against cytochrome bd oxidases which are only found in prokaryotes and are therefore promising new targets, using madecassic acid and a set of synthetically modified derivatives. Our work shows that madecassic acid and its derivatives can block activity of these enzymes, while phenotypic effects in membrane and whole organism assays are more complex, consistent with modulation of multiple pathways depending upon molecular structure. This provides a new route to ursane-based antibacterial action while highlighting the importance of chemical modifications in fine-tuning biological activity of natural products.
| Item Type: | Article |
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| DOI/Identification number: | 10.1039/d5md01116g |
| Subjects: |
Q Science > QD Chemistry Q Science > QR Microbiology |
| Institutional Unit: |
Schools > School of Natural Sciences Schools > School of Natural Sciences > Biosciences Schools > School of Natural Sciences > Chemistry and Forensic Science |
| Former Institutional Unit: |
There are no former institutional units.
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| Funders: |
Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Engineering and Physical Sciences Research Council (https://ror.org/0439y7842) |
| Depositing User: | Mark Shepherd |
| Date Deposited: | 22 Jan 2026 10:08 UTC |
| Last Modified: | 28 Jan 2026 14:46 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/112819 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Boughton, Ryan A..
| Creator's ORCID: | |
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| CReDIT Contributor Roles: |
Joiner, Guy.
| Creator's ORCID: | |
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| CReDIT Contributor Roles: |
Garrett, Michelle D..
| Creator's ORCID: |
 https://orcid.org/0000-0002-3939-1673
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| CReDIT Contributor Roles: |
Serpell, Christopher J..
| Creator's ORCID: |
https://orcid.org/0000-0002-2848-9077
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| CReDIT Contributor Roles: |
Robinson, Gary K..
| Creator's ORCID: |
https://orcid.org/0000-0003-2660-7778
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| CReDIT Contributor Roles: |
Shepherd, Mark.
| Creator's ORCID: |
https://orcid.org/0000-0002-7472-2300
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| CReDIT Contributor Roles: |
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