Publication: An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.
Loading...
Identifiers
Date
2015-06-20
Authors
Olmo, Francisco
Urbanová, Kristína
Rosales, Maria Jose
Martín-Escolano, Ruben
Sánchez-Moreno, Manuel
Marín, Clotilde
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.
Description
Journal Article;
MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiparasitic Agents
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Cercopithecidae::Cercopithecinae::Cercopithecus::Cercopithecus aethiops
Medical Subject Headings::Diseases::Parasitic Diseases::Protozoan Infections::Euglenozoa Infections::Trypanosomiasis::Chagas Disease
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred BALB C
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Microscopy
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Nitro Compounds::Nitroimidazoles
Medical Subject Headings::Diseases::Parasitic Diseases::Parasitemia
Medical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Parasites
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Superoxide Dismutase
Medical Subject Headings::Organisms::Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Vero Cells
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiparasitic Agents
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Cercopithecidae::Cercopithecinae::Cercopithecus::Cercopithecus aethiops
Medical Subject Headings::Diseases::Parasitic Diseases::Protozoan Infections::Euglenozoa Infections::Trypanosomiasis::Chagas Disease
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred BALB C
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Microscopy
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Nitro Compounds::Nitroimidazoles
Medical Subject Headings::Diseases::Parasitic Diseases::Parasitemia
Medical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Parasites
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Superoxide Dismutase
Medical Subject Headings::Organisms::Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Vero Cells
DeCS Terms
CIE Terms
Keywords
Anti-chagasic, Chemotherapy, Trypanosomiasis, Hydroxyphthalazine derivatives, Antiparasitarios, Enfermedad de chagas, Citometría de flujo, Concentración 50 inhibidora, Imagen por resonancia magnética, Ratones consanguíneos BALB C, Microscopía, Parásitos, Células vero
Citation
Olmo F, Urbanová K, Rosales MJ, Martín-Escolano R, Sánchez-Moreno M, Marín C. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase. Int J Parasitol Drugs Drug Resist. 2015 ; 5(3):110-6