Background: Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives.
Objective: The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy.
Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes.
Results: Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells.
Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1573406414666181005145042 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.
ACS Chem Biol
January 2025
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.
We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .
View Article and Find Full Text PDFCurrent strategies in design and synthesis of antifungals hybrid and chimeric diazine derivatives.
Bioorg Med Chem
January 2025
Alexandru Ioan Cuza University of Iasi, Faculty of Chemistry, Bd. Carol 11, 700506 Iasi, Romania. Electronic address:
In the last decades fungal infections became a major threat to human health having an unacceptably occurrence, a high rate of mortality and the number of patients at risk for these infections continue to increase every year. An effective, modern and very useful strategy in antifungal therapy is represented by the use of chimeric and hybrid drugs, most of them being with azaheterocycle skeleton. In this review, we present an overview from the last five years of the most representative achievements in the field of chimeric and hybrid diazine derivatives with antifungal properties.
View Article and Find Full Text PDFIn vitro and in vivo Investigations of 4-Substituted 2-Phenylquinazoline derivatives as multipotent ligands for the treatment of Alzheimer's disease.
Bioorg Chem
January 2025
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Central University of Punjab, Bathinda, India, 151401. Electronic address:
The pathology of Alzheimer's disease (AD) is complex due to its multifactorial nature and single targeting drugs proved inefficient. A series of novel 4-N-substituted-2-phenylquinazoline derivatives was designed and synthesized as potential multi-target directed ligands (MTDLs) through dual inhibition of AChE and MAO-B enzymes along with Aβ aggregation inhibition for the treatment of AD. Two compounds in the series, VAV-8 and VAV-19 were found to be the most potent inhibitors of both AChE and MAO-B enzymes and moderate inhibitor of Aβ, with good thermodynamic stability at the binding pocket of the enzymes.
View Article and Find Full Text PDFMolecular Dynamics Insights into Peptide-Based Tetrodotoxin Delivery Nanostructures.
Molecules
December 2024
Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM 87131, USA.
Tetrodotoxin (TTX), a potent Site-1 sodium channel blocker (S1SCB), offers highly effective local anesthetic properties with minimal addiction potential. To fully leverage TTX's capabilities as a local anesthetic, it is crucial to develop a drug delivery system that balances its systemic toxicity with its therapeutic efficacy. Recent studies have shown that peptide mixtures, derived from fragments of Site-1 sodium channel proteins and enhanced with hydrophobic tails (designated MP1 and MP2), can self-assemble into nanostructures that exhibit remarkable sustained-release capabilities for TTX.
View Article and Find Full Text PDFCopper-Catalyzed Domino Annulation of Isoselenocyanates: A Pathway to Structurally Diverse , Se-Bis-Heterocyclic, and Fused Heterocyclic Compounds.
J Org Chem
January 2025
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, People's Republic of China.
A copper-catalyzed domino addition/cyclization reaction was developed to synthesize novel benzoselenazole-linked 1,2,3-triazole and tetracyclic fused 12-benzo[4,5]selenazole[2,3-]quinazolin-12-one derivatives from isoselenocyanates. This domino reaction efficiently constructed multiple new chemical bonds in a single step, forming either four (one C-Se and three C-) or three (one C-Se and two C-) bonds. The reaction offers several key advantages, including mild conditions, broad substrate compatibility, and straightforward and safe operation.
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!