AI Article Synopsis
- - A set of new benzothiozinone (BTZ) derivatives was created and tested for their effectiveness against tuberculosis, showing significantly improved activity compared to earlier versions.
- - The study found that changing the ring structure of the compounds to either alkynyl or vinyl linkers not only enhanced antimycobacterial potency but also influenced their metabolic stability and overall drug characteristics.
- - Two specific compounds, A1 and A11, exhibited low minimum inhibitory concentrations (MICs) and better metabolic stability, with A11 proving effective in treating acute tuberculosis in a mouse model.
Article Abstract
A series of novel benzothiozinone (BTZ) derivatives were designed, prepared and evaluated for antituberculosis activity. Specifically, the BTZ pharmacophore is retained and the previous heterocyclic ring linker is replaced by alkynyl or vinyl linker, the resulting compounds displayed about 5-fold improved antimycobacterial activity. We further revealed that the linker attached tail group affects the compound metabolic stability, potency and other drug like properties. This work led to the discovery of two compounds (A1 and A11) with acceptable low MICs and improved metabolic stability. The representative compound A11 demonstrated bactericidal efficacy in an acute TB infection mouse model.
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| http://dx.doi.org/10.1016/j.ejmech.2023.115976 | DOI Listing |
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