is a protozoan parasite that causes Chagas disease in humans. The current antichagasic drugs nifurtimox and benznidazole have inconveniences of toxicity; therefore, the search for alternative therapeutic strategies is necessary. The present study reports the synthesis, drug-likeness predictions, and in vitro anti-trypanosome activity of a series of 14 quinazoline 2,4,6-triamine derivatives. All compounds were tested against (epimastigotes and trypomastigotes) and in HFF1 human foreskin fibroblasts. The bioassays showed that compounds - containing nitrobenzoyl substituents at 6-position of the quinazoline 2,4,6-triamine nucleus were the most potent on its antiprotozoal activity. The effect was observed at 24 h and it was preserved for at least 5 days. Also, compounds - were not toxic to the human control cells, showing high selectivity index. The quinazoline nitro derivatives have potential use as antichagasic agents.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435156 | PMC |
| http://dx.doi.org/10.3390/molecules29184501 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Expression Analysis of Thirteen Genes in Response to Nifurtimox and Benznidazole in Mexican Isolates of Trypanosoma cruzi by Digital PCR.
Acta Parasitol
January 2025
Edificio D, Facultad de Ciencias Químicas, LADISER Inmunología y Biología Molecular, Universidad Veracruzana, Orizaba, Veracruz, México.
Despite being the most relevant and critical option for managing Chagas disease, pharmacological therapy is currently limited by the availability of only two drugs, benznidazole and nifurtimox. Their effectiveness is further restricted in the chronic phase of the infection, as they induce severe side effects and require prolonged treatment. Additionally, the use of these drugs can lead to the emergence of substantial resistance problems, compounded by the potential natural resistance of some parasite isolates.
View Article and Find Full Text PDFDesign, synthesis, in vitro and in vivo trypanosomaticidal efficacy of novel 5-nitroindolylazines.
Eur J Med Chem
December 2024
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido, 080-8555, Japan.
Leishmaniasis and trypanosomiasis rank among lethal vector-borne parasitic diseases that are endemic in tropical and sub-tropical countries. There are currently no preventive vaccines against them, and once diagnosed, a handful of less effective drugs clinically accessible are the only therapeutic options offered to treat these ailments. And although curable, the eradication and elimination of these diseases are hampered by the emergence of multidrug-resistant strains of the causal pathogens.
View Article and Find Full Text PDFExploring Quinazoline Nitro-Derivatives as Potential Antichagasic Agents: Synthesis and In Vitro Evaluation.
Molecules
September 2024
Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
is a protozoan parasite that causes Chagas disease in humans. The current antichagasic drugs nifurtimox and benznidazole have inconveniences of toxicity; therefore, the search for alternative therapeutic strategies is necessary. The present study reports the synthesis, drug-likeness predictions, and in vitro anti-trypanosome activity of a series of 14 quinazoline 2,4,6-triamine derivatives.
View Article and Find Full Text PDFStructure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.
Molecules
September 2024
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (FCQ-UNC), Haya de la Torre y Medina Allende, Córdoba 5000, Argentina.
Cruzipain (CZP), the major cysteine protease present in , the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti- activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages.
View Article and Find Full Text PDFStructure-Metabolism Relationships of Benzimidazole Derivatives with anti-Trypanosoma cruzi Activity for Chagas Disease.
ChemMedChem
October 2024
Laboratory of Synthetic Organic Chemistry, Institute of Chemistry, State University of Campinas (Unicamp), Campinas-SP, 13084-971, Brazil.
This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies.
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!