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结构异构化影响金刚烷基异恶唑加合物的抗结核活性。

Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts.

作者信息

Lu Yucheng, Partleton Daniel, Gugu Filibus M, Alhejaili Ahmed Y G, Norris Samuel, Harburn J Jonathan, Gill Jason H, Sellars Jonathan D, Brown Alistair K

机构信息

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Department of Microbiology, Plateau State University Bokkos, Jos, Nigeria.

出版信息

J Enzyme Inhib Med Chem. 2025 Dec;40(1):2502600. doi: 10.1080/14756366.2025.2502600. Epub 2025 May 21.

DOI:10.1080/14756366.2025.2502600
PMID:40396606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12096669/
Abstract

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 whilst displaying limited toxicity in comparison to other antitubercular agents. Indications from our genetic and biochemical studies suggest that these structurally similar pharmacophores bind to different proteins within , 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 .

摘要

尽管人们努力寻找有效的治疗方法来根除结核病（TB），但它仍然是一个全球性威胁。耐药细菌种类的增加使得新药的发现备受期待。利用先前有效的结构是一种可以用来开发新型化合物系列以应对这一日益严重问题的方法。本研究试图重新审视两种这样的化合物，异烟肼（ISO）和SQ109，它们先前已被证明在结核病治疗中有效。与其他抗结核药物相比，SQ109-ISO杂合化合物对药物敏感菌和耐药菌均显示出明显的活性，同时毒性有限。我们的基因和生化研究表明，这些结构相似的药效基团与结核分枝杆菌内的不同蛋白质结合，这突出了在生产区域异构体类似物时需要仔细考虑，并且利用先前有效的结构是开发有前景的抗结核新药的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/65ac81e12a36/IENZ_A_2502600_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/2a0d58fc41ca/IENZ_A_2502600_F0001_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/b401ac7c9dbf/IENZ_A_2502600_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/7e2294e1f174/IENZ_A_2502600_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/2630ad5de906/IENZ_A_2502600_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/aee685f5bada/IENZ_A_2502600_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/0e74146ad24f/IENZ_A_2502600_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/7a618d892963/IENZ_A_2502600_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/feb8dff8869c/IENZ_A_2502600_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/65ac81e12a36/IENZ_A_2502600_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/2a0d58fc41ca/IENZ_A_2502600_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/9fd1ddcc78f5/IENZ_A_2502600_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/b401ac7c9dbf/IENZ_A_2502600_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/7e2294e1f174/IENZ_A_2502600_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/2630ad5de906/IENZ_A_2502600_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/aee685f5bada/IENZ_A_2502600_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/0e74146ad24f/IENZ_A_2502600_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/7a618d892963/IENZ_A_2502600_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/feb8dff8869c/IENZ_A_2502600_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67e4/12096669/65ac81e12a36/IENZ_A_2502600_F0009_C.jpg

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