Development of Thieno[2,3-b]pyridin-6(7H)-one derivatives against drug-resistant Mycobacterium tuberculosis.
Bioorganic & medicinal chemistry·
- DOI
- 10.1016/j.bmc.2026.118663
- PMID
- 41990416
- PMCID
- —
- OpenAlex
- W7153450963
- Study type
- Journal article
- Publisher
- Publisher unavailable
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The compounds represent potential hit candidates for developing novel antitubercular agents effective against drug-resistant tuberculosis, addressing a critical need for new therapeutic options.
Structured evidence summary
Research question
The study aimed to develop and evaluate thieno[2,3-b]pyridin-6(7H)-one derivatives as potential antitubercular agents against drug-resistant Mycobacterium tuberculosis.
Study design
This was a drug development study combining rational chemical design with in vitro antimicrobial testing, whole-genome sequencing of resistant mutants, and resistance mechanism investigations using overexpression assays.
Population and setting
The study tested compounds against autoluminescent Mycobacterium tuberculosis H37Ra laboratory strains, clinical drug-resistant isolates, and intracellular bacteria in macrophages.
Main findings
Four compounds demonstrated minimum inhibitory concentrations below 0.5 μg/mL against Mtb H37Ra, comparable to or exceeding rifampin. Lead compound 3a showed activity against clinical drug-resistant isolates and intracellular bacteria, favorable microsomal stability, and a narrow antibacterial spectrum. Resistance to these derivatives was mediated through IdsA2-dependent isoprenoid biosynthesis and PEPCK-governed gluconeogenesis pathways.
Public-health relevance
The compounds represent potential hit candidates for developing novel antitubercular agents effective against drug-resistant tuberculosis, addressing a critical need for new therapeutic options.
Important limitations
This summary is limited to the supplied single-article abstract and metadata. Full assessment of study limitations, including sample sizes, replication status, in vivo validation, and clinical translatability, requires review of the complete published paper.
GIDS interpretation
This article was classified under Tuberculosis and Antimicrobial Resistance topics in GIDS, making it discoverable through disease-specific and thematic searches within the surveillance platform. The classification reflects the content focus rather than epidemiological signal detection.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 5 auditable classifier relationships to diseases, places, topics, and study design.