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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2025.2502600
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1475-6366
1475-6374