AI Article Synopsis
- The study addresses the urgent issue of drug-resistant tuberculosis, emphasizing the necessity for new drug candidates to improve treatment options.
- Researchers discovered a potent compound, (4-benzylpiperidin-1-yl)(1-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-4-yl)methanone, through high-throughput screening, which showed effectiveness against both drug-resistant and drug-susceptible strains of TB.
- Analysis of resistant mutant strains identified mutations in the DprE1 gene, suggesting a new avenue for drug development and highlighting the potential of the novel oxadiazole structure as a valuable tool in TB treatment.
Article Abstract
The continuing prevalence of drug-resistant tuberculosis threatens global TB control programs, highlighting the need to discover new drug candidates to feed the drug development pipeline. In this study, we describe a high-throughput screening hit (4-benzylpiperidin-1-yl)(1-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-4-yl)methanone () as a potent antitubercular agent. Structure-activity guided synthesis led to the discovery of several analogs with high potency. was found to have promising potency against many drug-resistant strains, as well as drug-susceptible clinical isolates. It also showed cidality against growing in host macrophages. Whole genome sequencing of genomic DNA from resistant mutants raised to revealed mutations in decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1). This novel oxadiazole scaffold expands the set of chemical tools for targeting a well-validated pathway to treat tuberculosis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510505 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.3c00295 | DOI Listing |
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