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Novel isoxazole thiophene-containing compounds active against Mycobacterium tuberculosis.
Bioorg Med Chem Lett
January 2025
Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research, La Jolla, CA 92037, United States. Electronic address:
Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC = 1.
View Article and Find Full Text PDFInhibitors of NADH-O-methylquinone compound a class of antitubercular drugs.
Mol Divers
January 2025
Department of Laboratory Medicine, The Fourth People's Hospital of Nanhai District of Foshan City, Foshan, 528000, Guangdong, China.
Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level.
View Article and Find Full Text PDFAdditive Effects of Glutathione in Improving Antibiotic Efficacy in HIV- Co-Infection in the Central Nervous System: A Systematic Review.
Viruses
January 2025
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction.
View Article and Find Full Text PDFComparative Performance of Ante-Mortem Diagnostic Assays for the Identification of -Infected Domestic Dogs ().
Pathogens
January 2025
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH25 9RG, UK.
The domestic dog () is a competent host for () infection but no ante mortem diagnostic tests have been fully validated for this species. The aim of this study was to compare the performance of ante mortem diagnostic tests across samples collected from dogs considered to be at a high or low risk of sub-clinical infection. We previously tested a total of 164 dogs at a high risk of infection and here test 42 dogs at a low risk of infection and 77 presumed uninfected dogs with a combination of cell-based and/or serological diagnostic assays previously described for use in non-canid species.
View Article and Find Full Text PDFCytokine and Chemokine Responses of Peripheral Blood Mononuclear Cells from Dogs Infected with .
Pathogens
December 2024
Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH25 9RG, UK.
Mycobacterial infections are an important emerging zoonosis in companion animals for which diagnostic options remain imperfect, and the canine immunological response to these infections has been poorly investigated. We sought to further define the cellular response of peripheral blood mononuclear cells (PBMCs) from dogs infected with , as determined using a commercial interferon-gamma response assay (IGRA). To this end, PBMCs from healthy or infected dogs were collected.
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