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Targeting InhA in drug-resistant Mycobacterium tuberculosis: potent antimycobacterial activity of diaryl ether dehydrozingerone derivatives.
Arch Microbiol
January 2025
Clinical Microbiology and PK-PD Division, CSIR-Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, J&K, 190005, India.
Tuberculosis (TB) remains a major global threat, with 10 million new cases and 1.5 million deaths each year. In multidrug-resistant tuberculosis (MDR-TB), resistance is most commonly observed against isoniazid (INH) and rifampicin (RIF), the two frontline drugs.
View Article and Find Full Text PDFPhenytoin toxicity caused by a drug-to-drug interaction between phenytoin and antitubercular therapy.
BMJ Case Rep
January 2025
Internal Medicine, All India Institute of Medical Sciences - Rishikesh, Rishikesh, Uttarakhand, India.
Phenytoin is one of the most used antiepileptic drugs. Isoniazid, a first-line antitubercular drug, blocks the CYP2C19 enzyme, preventing phenytoin from being metabolised. Concomitant use of phenytoin and isoniazid predisposes to phenytoin toxicity.
View Article and Find Full Text PDFSafety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.
Lancet Microbe
December 2024
Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU Munich, Germany; German Center for Infection Research, Munich Partner Site, Munich, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection, and Pandemic Research, Munich, Germany; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address:
Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.
Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.
Organocatalysed synthesis of -(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4)-yl)isonicotinamide: computational, electrochemical, drug-likeness and antimicrobial studies.
3 Biotech
January 2025
Peptide and Medicinal Chemistry Research Laboratory, Department of Chemistry, Rani Channamma University, P-B, NH-4, Belagavi, 591 156 India.
Unlabelled: We have developed novel and sustainable homogeneous catalysts employing Glutamic acid (Glu) as a biodegradable and eco-friendly organocatalyst for the synthesis of -(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4)-yl)isonicotinamide derivatives (-) via multicomponent reactions (MCRs) of isatoic anhydride, isoniazid and heteroaromatic/aromatic aldehyde in ethanol on oil bath stirring at 60 °C. Selected final product homogeneity was examined by various spectroscopic techniques such as C-, H- NMR, FT-IR and LC-MS. For the first time, herein investigated electrochemical behavior of selected derivatives (-) using cyclic voltammetry method.
View Article and Find Full Text PDFThe new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis.
J Enzyme Inhib Med Chem
December 2025
Department of Organic Chemistry, Medical University of Lublin, Lublin, Poland.
The ever-increasing drug-resistant tuberculosis (TB) has invigorated the focus on the discovery and development of novel therapeutic agents and treatment options. Thiazolidinone-based compounds have shown good antitubercular properties . Here, we report the design and synthesis of a number of new derivatives inspired by the structure of thiazolidine-2,4-dione (TZD).
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