Search results for "trypanosoma"
showing 10 items of 87 documents
Inhibition of Trypanosoma cruzi growth by medical plant extracts
2002
This study describes the screening of extracts obtained from 18 plants and two fungi used in the Chinese and Mediterranean traditional medicines on epimastigote forms of Trypanosoma cruzi. The extracts were tested against epimastigote of T. cruzi Bra C15C2 clone in vitro at 27 degrees C and at a concentration of 250 microg/ml in axenic culture. Angelica dahurica, A. pubescens, A. sinensis, Astragalus membranaceus, Coptis chinensis, Haplophyllum hispanicum, Phellodendron amurense, Poria cocos, Ranunculus sceleratus and Scutellaria baicalensis showed significant effects against the parasite with a percentage of growth inhibition between 20 and 100%. C. chinensis and R. sceleratus showed the g…
Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009
2011
INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period. METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time fro…
Does Autoimmunity Play a Role in the Immunopathogenesis of Vasculitis Associated With Chronic Chagas Disease?
2021
Chagas disease (CD) is a chronic systemic vector-borne infection caused by the protozoan Trypanosoma cruzi. It has spread from Latin America through migration, becoming a global issue (Perez-Molina and Molina, 2018). Its prevalence is ∼7 million people worldwide, of whom 30-40% will develop severe chronic complications such as cardiomyopathy or megaviscerae, with a considerable impact on morbimortality (WHO, 2020; WHO, 2021). The parasite is transmitted after metacyclic trypomastigotes in the feces of a triatomine insect enter the host through the bite wound. They penetrate cells and transform into amastigotes, where they multiply by binary fission and differentiate again into circulating t…
TRYPANOSOMES OF SOME FENNOSCANDIAN BIRDS
1994
Linear measurements and derived indices of trypanosomes from species of Fennoscandian birds were compared to those reported form Trypanosoma avium, T. everetti, T. ontarioensis and T. paddae. The trypanosomes encountered in the Fennoscandian birds were identified as T. avium from Tengmalm's owl Aegolius funereus and the pied flycatcher Ficedula hypoleuca, T. everetti from the great tit Parus major and collared flycatcher F. albicollis and T. ontarioensis from the collared flycatcher; T. paddae was not seen.
Identifying four Trypanosoma cruzi I isolate haplotypes from different geographic regions in Colombia
2007
Abstract Trypanosoma cruzi has been classified into the groups T. cruzi I and T. cruzi II. The latter is subdivided into five smaller lineages based on multilocus enzyme electrophoresis and random amplified polymorphic DNA, designated as IIa-IIe, which shows correspondence with rRNA/mini-exon lineages. Twelve previously characterised T. cruzi isolates from different hosts, including humans, Didelphis marsupialis, and triatomines were analysed to establish genetic variability in T. cruzi group T. cruzi I isolates from different geographical regions of Colombia. DNA samples were sequenced based on the mini-exon gene intergenic region. Sequences were analysed using Clustal W, Staden 1.5 and ME…
Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichag…
2012
Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and benznidazole, is far from satisfactory and therefore the development of new antichagasic compounds remains an important goal. On the basis of antichagasic properties previously described for some 1,2-disubstituted 5-nitroindazolin-3- ones (21, 33) and in order to initiate the optimization of activity of this kind of compounds, we have prepared a series of related analogs (22-32, 34-38, 58 and 59) and tested in vitro these products against epimastigote forms of Trypanosoma cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) and 2-benzyl-1-butyl (24) derivatives have shown high trypanocidal activity and low un…
Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal…
2013
The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 subs…
Tuning and Predicting Biological Affinity: Aryl Nitriles as Cysteine Protease Inhibitors
2012
A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.
Structure, interdomain dynamics, and pH-dependent autoactivation of pro-rhodesain, the main lysosomal cysteine protease from African trypanosomes
2021
AbstractRhodesain is the lysosomal cathepsin L-like cysteine protease ofT. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Lysosomal cathepsins are expressed as zymogens with an inactivating pro-domain that is cleaved under acidic conditions. A structure of the uncleaved maturation intermediate from a trypanosomal cathepsin L-like protease is currently not available. We thus established the heterologous expression ofT. brucei rhodesiensepro-rhodesain inE. coliand determined its crystal structure. The trypanosomal pr…
The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines
2021
Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense which seriously affects human health in Africa. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work herein describes the design and syntheses of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines, with compound 13, the 4-(2-methoxyphenyl)-6-(pyridine-3-yl)pyrimidin-2-amine demonstrating an IC50 value of 0.38 μM and a promising off-target ADME-Tox profile in vitro. In silico molecular target investigations showed rhodesain to be a pu…