Identification of compounds that target metabolically diverse subpopulations of Mycobacterium tuberculosis (Mtb) may contribute to shortening the course of treatment for tuberculosis. This study screened 270,000 compounds from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed in vitro by a combination of four host-relevant stresses. Evaluation of 166 confirmed hits led to detailed characterization of 19 compounds for potency, specificity, cytotoxicity, and stability. Compounds representing five scaffolds depended on reactive nitrogen species for selective activity against NR Mtb, and two were stable in the assay conditions. Four novel scaffolds with activity against replicating (R) Mtb were also identified. However, none of the 19 compounds was active against Mtb in both NR and R states. There was minimal overlap between compounds found active against NR Mtb and those previously identified as active against R Mtb, supporting the hypothesis that NR Mtb depends on distinct metabolic pathways for survival.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acsinfecdis.5b00025 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Evaluation of Boron-Containing Heterocyclic Compounds with Antimicrobial and Anticancer Activities.
Molecules
February 2025
School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil.
Organoboron compounds, especially those containing boronic acid and benzoxaborole in their structure, have been gaining prominence in medicinal chemistry, following the FDA approval of tavaborole for the treatment of onychomycosis and bortezomib for multiple myeloma. The antimicrobial and anticancer effects of organoboron compounds motivate the investigation of the effects of the novel derivatives described here. A total of fourteen new boronic derivatives were synthesized and characterized using analytical methods.
View Article and Find Full Text PDFDprE1 Inhibitors: An insight into the recent developments and synthetic approaches.
Eur J Pharm Sci
March 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria; Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
In the current medical era, the proliferation and dissemination of drug-resistant strains of Mycobacterium tuberculosis continue to pose a significant worldwide health hazard, necessitating the development of new and innovative medications to combat tuberculosis. Decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) is a crucial enzyme for cell wall synthesis in Mycobacterium tuberculosis (Mtb). Its importance is due to its eminent contribution in forming lipoarabinomannan and arabinogalactan.
View Article and Find Full Text PDFExploring the Anti-tubercular Potential of 2-(1H-Pyrazol-1-yl) Pyrimidine: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.
Chem Biodivers
March 2025
Birla Institute of Technology and Science - Pilani Campus: Birla Institute of Technology & Science Pilani, Pharmacy, Vidya Vihar campus, Pilani, INDIA.
We designed and synthesized pyrazolyl pyrimidine containing derivatives and screened for anti-mycobacterial activity. Different spectral techniques like HRMS, 1H, and 13C NMR are deployed for the structural confirmation of the final derivatives. Final compounds were screened against the Mycobacterium tuberculosis (Mtb) H37Rv strain.
View Article and Find Full Text PDFTLR4-mediated endoplasmic reticulum stress regulates pyroptosis in macrophages infected with the Bacillus Calmette-Guérin mycobacterial.
Int Immunopharmacol
March 2025
School of Life Sciences, Ningxia University, Yinchuan 750021, China; Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China. Electronic address:
Tuberculosis results from Mycobacterium tuberculosis (Mtb) infection. Immune responses controlled by Toll-like receptor 4 (TLR4) are closely associated with the host response to pathogens, including Mtb. NLRP3 inflammasome-mediated pyroptosis forms a significant part of the inflammatory response during Mtb infection, and endoplasmic reticulum stress (ERS) is implicated in the activation of the NLRP3 inflammasome.
View Article and Find Full Text PDFA Perplexing Case Highlighting the Diagnostic Conundrum of Miliary Tuberculosis Mimicking Sarcoidosis and Progressing Into Hemophagocytic Lymphohistiocytosis.
Cureus
February 2025
Internal Medicine, AdventHealth, Orlando, USA.
Establishing the diagnosis of miliary tuberculosis (TB) can be challenging due to the heterogeneous clinical presentations and low sensitivity of diagnostic tests. Miliary TB shares overlapping clinical, radiological, and histopathological features with other chronic granulomatous diseases, such as sarcoidosis, often posing a significant diagnostic challenge for clinicians. A 36-year-old male from Haiti presented with a four-month history of recurrent fever, dry cough, night sweats, and weight loss.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!