Pyrazole and Triazole Derivatives as Mycobacterium tuberculosis UDP-Galactopyranose Inhibitors

UDP-galactopyranose mutase (UGM) is an essential enzyme involved in the bacterial cell wall synthesis, and is not present in mammalian cells. Thus, UGM from ( ) represents a novel and attractive drug target for developing antituberculosis agents. A pyrazole-based compound, , was previously identifie...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-02, Vol.15 (2), p.197
Main Authors: Ahmed, Dalia M, Chen, Jeffrey M, Sanders, David A R
Format: Article
Language:English
Subjects:
antituberculosis
enzyme kinetics
Enzymes
Hydrogen bonds
Hypotheses
inhibitors
pyrazoles
Solvents
Spectrum analysis
triazoles
Tuberculosis
UDP-galactopyranose mutase
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Summary:UDP-galactopyranose mutase (UGM) is an essential enzyme involved in the bacterial cell wall synthesis, and is not present in mammalian cells. Thus, UGM from ( ) represents a novel and attractive drug target for developing antituberculosis agents. A pyrazole-based compound, , was previously identified as a mixed inhibitor of UGM which targets an allosteric site. To understand more about the structure activity relationship around the scaffold as a UGM inhibitor, thirteen pyrazoles and triazole analogues were synthesized and tested against both UGM and in vitro. While the introduced structural modifications to did not improve the antituberculosis activity, most of the compounds showed UGM inhibitory activity. Interestingly, the pyrazole derivative showed a competitive model for UGM inhibition with improved Ki value of 51 ± 4 µM. However, the same compound did not inhibit the growth of .
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15020197