AI Article Synopsis
- A series of hybrid molecules featuring thienopyrimidinones and thiouracil were created and tested for their effectiveness against Mycobacterium tuberculosis, with some compounds showing promising antitubercular activity against both dormant and active stages of the bacteria.
- Research identified structural modifications on one compound, leading to a new derivative that also demonstrated significant activity, suggesting the potential for further optimization.
- Additionally, cytotoxicity studies indicated these compounds were non-toxic, and docking studies showed that one compound effectively bound to mycobacterial pantothenate synthetase, laying groundwork for the development of new antimycobacterial agents.
Article Abstract
A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 μg/mL, 12-35 μM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 μg/mL, 41 μM) as well as active (MIC 25.4 μg/mL, 45 μM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15. Cytotoxicity studies revealed that these molecules were non-toxic. The docking study of the compound 15 showed that there was binding with the active site of mycobacterial pantothenate synthetase. Further docking studies led to the synthesis of the compounds 16 and 17 and the antitubercular activity screening results showed that these compounds have significant antitubercular activity. The compounds 15-18 (MIC 11-29 μg/mL, 19-51 μM) can be used as starting points for further optimization. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures and the present results will be very useful in the development of a new class of antimycobacterial agents.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2017.01.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chemoprotective Mechanism of Sodium Thiosulfate Against Cisplatin-Induced Nephrotoxicity Is via Renal Hydrogen Sulfide, Arginine/cAMP and NO/cGMP Signaling Pathways.
Int J Mol Sci
January 2025
Department of Animal Experimentation, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra P.O. Box LG581, Ghana.
Cisplatin is a common and highly effective chemotherapeutic agent whose nephrotoxic side effect is well-characterized. Sodium thiosulfate (STS), an FDA-approved hydrogen sulfide (HS) donor drug, is emerging as a chemoprotective agent against cisplatin-induced nephrotoxicity (CIN). In this study, we investigated the chemoprotective mechanism of STS in a rat model of CIN.
View Article and Find Full Text PDF4-Alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline Derivatives as New Heterocyclic Analogues of Indolo[2,3-]quinoxalines: Synthesis and Antitubercular Activity.
Int J Mol Sci
January 2025
Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Street, 22, Ekaterinburg 620137, Russia.
The synthetic approach based on a sequence of Buchwald-Hartwig cross-coupling and annulation through intramolecular oxidative cyclodehydrogenation has been used for the construction of novel 4-alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline derivatives. For the first time, these polycyclic compounds were evaluated for antimycobacterial activity, including extensively drug-resistant strains. A reasonable bacteriostatic effect against HRv was demonstrated.
View Article and Find Full Text PDFAntibacterial evaluation of antibiotic-coated titanium and stainless steel implants in orthopaedic application: a dip-coating approach.
J Orthop Surg Res
January 2025
Hamidiye Medicine Faculty, Department of Medical Biology, University of Health Sciences, Istanbul, Türkiye.
Background: Despite their biocompatibility, metal implants are susceptible to infections, leading to implant failure and patient complications. The purpose of this study was to investigate the antibacterial potential of antibiotic-coated titanium and stainless steel implants.
Methods: The study was designed as an experimental in vitro study, and it was conducted at the Department of Immunology of the University of Health Sciences, Istanbul/ Turkiye in January and February 2024.
Anti-Mycobacterial Activity of Bacterial Topoisomerase Inhibitors with Dioxygenated Linkers.
ACS Infect Dis
January 2025
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.
Developing new classes of drugs that are active against infections caused by is a priority for treating and managing this deadly disease. Here, we describe screening a small library of 20 DNA gyrase inhibitors and identifying new lead compounds. Three structurally diverse analogues were identified with minimal inhibitory concentrations of 0.
View Article and Find Full Text PDFRole of [18F]FDG - PET/CT Scan in Cervical Tuberculosis.
Indian J Nucl Med
November 2024
Department of General Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India.
Background: Distribution and quantification of extra-pulmonary tuberculosis and elicitation of response antitubercular therapy via F18-Fluorodeoxyglucose Positron Emission-based Tomography/ Computed Tomography(F18-FDG PET/CT).
Materials And Methods: This was a prospective Pilot study. In this study 30 patients of age between 15 to 36 years(mean 26.
Want 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!