Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts
Despite efforts to discover effective treatments to eradicate tuberculosis (TB), it remains a global threat. The increase in drug-resistant bacterial species has made the discovery of new drugs highly coveted. The utilisation of previous efficacious structures is one approach that can be employed to...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2025.2502600 |
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| author | Yucheng Lu Daniel Partleton Filibus M. Gugu Ahmed Y. G. Alhejaili Samuel Norris J. Jonathan Harburn Jason H. Gill Jonathan D. Sellars Alistair K. Brown |
| author_facet | Yucheng Lu Daniel Partleton Filibus M. Gugu Ahmed Y. G. Alhejaili Samuel Norris J. Jonathan Harburn Jason H. Gill Jonathan D. Sellars Alistair K. Brown |
| author_sort | Yucheng Lu |
| collection | DOAJ |
| description | Despite efforts to discover effective treatments to eradicate tuberculosis (TB), it remains a global threat. The increase in drug-resistant bacterial species has made the discovery of new drugs highly coveted. The utilisation of previous efficacious structures is one approach that can be employed to developing novel series of compounds to combat this ever-growing problem. This study sought to re-examine two such compounds, isoxyl (ISO) and SQ109, previously shown to be efficacious in TB treatment. SQ109-ISO hybrid compounds were shown to have demonstrable activity against both drug-sensitive and drug-resistant Mtb whilst displaying limited toxicity in vitro in comparison to other antitubercular agents. Indications from our genetic and biochemical studies suggest that these structurally similar pharmacophores bind to different proteins within Mtb, highlighting the need for careful consideration when producing regioisomeric analogues and that the utilisation of previous efficacious structures is a valid approach to developing promising novel drugs against Mtb. |
| format | Article |
| id | doaj-art-e86ebb26f44b46fd8a6a81c411ff1015 |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-e86ebb26f44b46fd8a6a81c411ff10152025-08-20T03:08:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.2502600Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adductsYucheng Lu0Daniel Partleton1Filibus M. Gugu2Ahmed Y. G. Alhejaili3Samuel Norris4J. Jonathan Harburn5Jason H. Gill6Jonathan D. Sellars7Alistair K. Brown8Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKChemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, UKSchool of Pharmacy, Faculty of Medical Sciences, King George VI Building, Newcastle upon Tyne, UKSchool of Pharmacy, Faculty of Medical Sciences, King George VI Building, Newcastle upon Tyne, UKBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKDespite efforts to discover effective treatments to eradicate tuberculosis (TB), it remains a global threat. The increase in drug-resistant bacterial species has made the discovery of new drugs highly coveted. The utilisation of previous efficacious structures is one approach that can be employed to developing novel series of compounds to combat this ever-growing problem. This study sought to re-examine two such compounds, isoxyl (ISO) and SQ109, previously shown to be efficacious in TB treatment. SQ109-ISO hybrid compounds were shown to have demonstrable activity against both drug-sensitive and drug-resistant Mtb whilst displaying limited toxicity in vitro in comparison to other antitubercular agents. Indications from our genetic and biochemical studies suggest that these structurally similar pharmacophores bind to different proteins within Mtb, highlighting the need for careful consideration when producing regioisomeric analogues and that the utilisation of previous efficacious structures is a valid approach to developing promising novel drugs against Mtb.https://www.tandfonline.com/doi/10.1080/14756366.2025.2502600MycobacteriumadamantylisoxylSQ109antitubercular |
| spellingShingle | Yucheng Lu Daniel Partleton Filibus M. Gugu Ahmed Y. G. Alhejaili Samuel Norris J. Jonathan Harburn Jason H. Gill Jonathan D. Sellars Alistair K. Brown Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts Journal of Enzyme Inhibition and Medicinal Chemistry Mycobacterium adamantyl isoxyl SQ109 antitubercular |
| title | Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts |
| title_full | Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts |
| title_fullStr | Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts |
| title_full_unstemmed | Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts |
| title_short | Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts |
| title_sort | structural isomerisation affects the antitubercular activity of adamantyl isoxyl adducts |
| topic | Mycobacterium adamantyl isoxyl SQ109 antitubercular |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2025.2502600 |
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