| enzyme architecture: remarkably similar transition states for triosephosphate isomerase-catalyzed reactions of the whole substrate and the substrate in pieces. | values of (k(cat)/k(m))gap for triosephosphate isomerase-catalyzed reactions of (r)-glyceraldehyde 3-phosphate and k(cat)/k(hpi)k(ga) for reactions of the substrate pieces glycolaldehyde and hpo3(2-) have been determined for wild-type and the following tim mutants: i172v, i172a, l232a, and p168a (tim from trypanosoma brucei brucei); a 208-tgag for 208-yggs loop 7 replacement mutant (l7rm, tim from chicken muscle); and, y208t, y208s, y208a, y208f and s211a (yeast tim). a superb linear logarithmic ... | 2014 | 24588650 |
| effect of probiotic (saccharomyces cerevisiae) supplementation on immune response in trypanosoma brucei brucei infected rats. | the immunomodulatory effect of the probiotic (saccharomyces cerevisiae) on trypanosoma brucei brucei infected rats was studied. thirty (30) rats divided into five groups (a-e) of 6 rats each were used for the study. groups a, b and c rats received feed supplemented with s. cerevisiae (at 0.08, 0.12 and 0.16/kg of feed, respectively) for the duration of the study. groups d and e diets were not supplemented. all the rats in the 5 groups were immunized with 0.3 ml of 10% sheep red blood cells (srbc ... | 2012 | 23047131 |
| infection with the secondary tsetse-endosymbiont sodalis glossinidius (enterobacteriales: enterobacteriaceae) influences parasitism in glossina pallidipes (diptera: glossinidae). | the establishment of infection with three trypanosoma spp (gruby) (kinetoplastida: trypanosomatidae), specifically trypanosoma brucei brucei (plimmer and bradford), t. b. rhodesiense (stephen and fatham) and t. congolense (broden) was evaluated in glossina pallidipes (austen) (diptera: glossinidae) that either harbored or were uninfected by the endosymbiont sodalis glossinidius (dale and maudlin) (enterobacteriales: enterobacteriaceae). temporal variation of co-infection with t. b. rhodesiense a ... | 2014 | 25527583 |
| antiprotozoal activity of ferroquine. | ferroquine (fq, ssr97193) is a synthetic compound currently in development for the treatment of malaria. the use of a single compound to treat several parasitoses would be very convenient for multi-infected patients and also for financial considerations. in this work, the activity of fq was investigated on three other protista parasites: kinetoplastidae (leishmania and trypanosoma) and the cosmopolite parasite trichomonas vaginalis. fq exhibited a significant in vitro activity on trypanosoma bru ... | 2013 | 23229318 |
| genetic and structural study of dna-directed rna polymerase ii of trypanosoma brucei, towards the designing of novel antiparasitic agents. | trypanosoma brucei brucei (tbb) belongs to the unicellular parasitic protozoa organisms, specifically to the trypanosoma genus of the trypanosomatidae class. a variety of different vertebrate species can be infected by tbb, including humans and animals. under particular conditions, the tbb can be hosted by wild and domestic animals; therefore, an important reservoir of infection always remains available to transmit through tsetse flies. although the tbb parasite is one of the leading causes of d ... | 2017 | 28265521 |
| proline metabolism is essential for trypanosoma brucei brucei survival in the tsetse vector. | adaptation to different nutritional environments is essential for life cycle completion by all trypanosoma brucei sub-species. in the tsetse fly vector, l-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. the procyclic (insect) stage of t. b. brucei uses l-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end pr ... | 2017 | 28114403 |
| conjugates of 2,4-dihydroxybenzoate and salicylhydroxamate and lipocations display potent antiparasite effects by efficiently targeting the trypanosoma brucei and trypanosoma congolense mitochondrion. | we investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-dhba)- and salicylhydroxamic acid (sham)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (lc). three series of lc conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f) to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of african trypanosomes (trypanosoma brucei brucei and t. congolense). this represente ... | 2017 | 28112515 |
| igm, lgg and il-6 profiles in the trypanosoma brucei brucei monkey model of human african trypanosomiasis. | human african trypanosomiasis (hat) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. however, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. a recent improved monkey model of hat using a trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. the objectives of the current study was to determine t ... | 2017 | 28099874 |
| trypanosoma brucei brucei traverses different biological barriers differently and may modify the host plasma membrane in the process. | trypanosoma brucei are extracellular hemoflagellate protozoan parasites and one of the causative agents of a devastating zoonotic disease called african trypanosomiasis. in humans, the disease is caused by trypanosoma brucei rhodensiense and trypanosoma brucei gambiense, which cross the blood brain barrier (bbb) causing neurological disorders which culminate in death if untreated. in some domestic animals and laboratory rodents, trypanosoma brucei brucei causes a disease similar to that in human ... | 2017 | 28011167 |
| trypanosoma brucei invasion and t-cell infiltration of the brain parenchyma in experimental sleeping sickness: timing and correlation with functional changes. | the timing of trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human african trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. | 2016 | 28002454 |
| immunomodulatory activity of buchholzia coriacea seed methanol extract on trypanosoma brucei brucei infected mice. | the seeds of buchholzia coriacea engler (capparaceae) are used in eastern nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. | 2017 | 27951754 |
| how do the alkaloids emetine and homoharringtonine kill trypanosomes? an insight into their molecular modes of action. | although trypanosoma brucei causes deadly sleeping sickness, the number of the registered medications is rather limited. some plant alkaloids are potent trypanocidal agents. | 2016 | 27912879 |
| structural and antitrypanosomal data of different carbasones of piperitone. | this article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2, 4-phenyl semicarbazone 3 and 4-phenyl thiosemicarbazone 4 prepared directly in situ from essential oil of cymbopogon schoenantus, whose gc-fid and gc-ms analysis revealed piperitone as major component (68.20%). the structures of hemi-synthesized compounds were confirmed by high throughput ir, ms, (1)h and (13)c nmr based spectrometric analysis. their antiparasitic activities were evaluated in vitro ... | 2016 | 27900358 |
| african trypanosomes and brain infection - the unsolved question. | african trypanosomes induce sleeping sickness. the parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. during the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. the brain, however, is a strictly controll ... | 2016 | 27739621 |
| anti-trypanosome effects of nutritional supplements and vitamin d3: in vitro and in vivo efficacy against trypanosoma brucei brucei. | previous publications suggest that nutritional supplements have anti-trypanosome activity in vitro, although apparent efficacy was not noted in vivo. this study was conducted by experimentally infecting mice with trypanosoma brucei brucei to assess the anti-trypanosome activity of various nutritional supplements with the hope of finding possible application in the treatment of african trypanosomiasis. | 2016 | 27579019 |
| testicular pathology, gonadal and epididymal sperm reserves of yankasa rams infected with experimental trypanosoma brucei brucei and trypanosoma evansi. | the study was conducted to evaluate the pathological effects of trypanosomosis on the testes, gonadal, and epididymal sperm reserves of yankasa rams for 98 days. | 2016 | 27536039 |
| reduced mitochondrial membrane potential is a late adaptation of trypanosoma brucei brucei to isometamidium preceded by mutations in the γ subunit of the f1fo-atpase. | isometamidium is the main prophylactic drug used to prevent the infection of livestock with trypanosomes that cause animal african trypanosomiasis. as well as the animal infective trypanosome species, livestock can also harbor the closely related human infective subspecies t. b. gambiense and t. b. rhodesiense. resistance to isometamidium is a growing concern, as is cross-resistance to the diamidine drugs diminazene and pentamidine. | 2016 | 27518185 |
| in vitro antitrypanosomal activity of the secondary metabolites from the mutant strain iu-3 of the insect pathogenic fungus ophiocordyceps coccidiicola nbrc 100683. | during the search for new antitrypanosomal drug leads, four antitrypanosomal compounds, of three depsipeptides and one nortriterpenoid, were isolated from cultures of the mutant strain iu-3 of the insect pathogenic fungus ophiocordyceps coccidiicola nbrc 100683. their structures were identified by the analysis of high resolution-electron ionization (hr-ei)-ms and hr-fab-ms, and (1)h- and (13)c-nmr spectra, including extensive two dimensional (2d)-heteronuclear nmr experiments, and comparison wit ... | 2016 | 27373660 |
| development of novel 1,4-benzodiazepine-based michael acceptors as antitrypanosomal agents. | novel 1,4-benzodiazepines, endowed with a michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against trypanosoma brucei brucei (ic50=5.29μm), coupled with a lack of cytotoxicity towards mammalian cells (tc50 >100μm). | 2016 | 27372809 |
| antitrypanosomal activity of a novel taccalonolide from the tubers of tacca leontopetaloides. | several taccalonolides with various bioactivities have been isolated from tacca species but no studies to isolate taccalonolides with anti-trypanosomal activity from tacca leontopetaloides have been reported. | 2016 | 27313159 |
| loop-mediated isothermal amplification for detection of the 5.8s ribosomal ribonucleic acid internal transcribed spacer 2 gene found in trypanosoma brucei gambiense. | the loop-mediated isothermal amplification (lamp) assay with its advantages of cost effectiveness, rapidity, and simplicity, has evolved as a sensitive and specific method for the detection of african trypanosomes. highly sensitive lamp reactions specific for trypanosoma brucei rhodesiense or that recognize but do not discriminate between trypanosoma brucei brucei, t. b. rhodesiense, trypanosoma brucei gambiense, and trypanosoma evansi have been developed. a sensitive lamp assay targeting the t. ... | 2017 | 27273643 |
| structure-function studies of hydrophobic residues that clamp a basic glutamate side chain during catalysis by triosephosphate isomerase. | kinetic parameters are reported for the reactions of whole substrates (kcat/km, m(-1) s(-1)) (r)-glyceraldehyde 3-phosphate (gap) and dihydroxyacetone phosphate (dhap) and for the substrate pieces [(kcat/km)e·hpi/kd, m(-2) s(-1)] glycolaldehyde (ga) and phosphite dianion (hpi) catalyzed by the i172a/l232a mutant of triosephosphate isomerase from trypanosoma brucei brucei (tbbtim). a comparison with the corresponding parameters for wild-type, i172a, and l232a tbbtim-catalyzed reactions shows that ... | 2016 | 27149328 |
| quinolone amides as antitrypanosomal lead compounds with in vivo activity. | human african trypanosomiasis (hat) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against trypanosoma brucei brucei since the lead compound ghq168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to ghq168 as well as to ... | 2016 | 27139467 |
| high frequency of (kinetoplastida: trypanosomatidae) type among (diptera: glossinidae) in a historic trypanosoma foci in north-eastern gabon: preliminary study. | human african trypanosomiasis became a neglected disease after the 1960s, when case numbers dropped dramatically. it again became a public health problem in sub-saharan africa at the end of the 1990s, when new cases were reported, notably in central africa, and specifically in gabon, where historic foci existed and new cases have been reported. therefore, the present study reports on an entomological survey conducted in may 2012 to determine the pathogenic trypanosome infection rate in tsetse fl ... | 2016 | 27113105 |
| an evaluation of minor groove binders as anti-trypanosoma brucei brucei therapeutics. | a series of 32 structurally diverse mgbs, derived from the natural product distamycin, was evaluated for activity against trypanosoma brucei brucei. four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for human and animal african trypanosomiases. moreover, sar indicates that the head group linking moiety is a significant modulator of biological activity. | 2016 | 27060763 |
| analytical purification of a 60-kda target protein of artemisinin detected in trypanosoma brucei brucei. | here we describe the isolation and purity determination of trypanosoma brucei (t. b.) brucei candidate target proteins of artemisinin. the candidate target proteins were detected and purified from their biological source (t. b. brucei lysate) using the diazirine-free biotinylated probe 5 for an affinity binding to a streptavidin-tagged resin and, subsequently, the labeled target proteins were purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (sds-page). we herein showed the e ... | 2015 | 26958596 |
| de novo genome assembly shows genome wide similarity between trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | trypanosoma brucei is a eukaryotic pathogen which causes african trypanosomiasis. it is notable for its variant surface glycoprotein (vsg) coat, which undergoes antigenic variation enabled by a large suite of vsg pseudogenes, allowing for persistent evasion of host adaptive immunity. while trypanosoma brucei rhodesiense (tbr) and t. b gambiense (tbg) are human infective, related t. b. brucei (tbb) is cleared by human sera. a single gene, the serum resistance associated (sra) gene, confers tbr it ... | 2016 | 26910229 |
| illuminating the prevalence of trypanosoma brucei s.l. in glossina using lamp as a tool for xenomonitoring. | as the reality of eliminating human african trypanosomiasis (hat) by 2020 draws closer, the need to detect and identify the remaining areas of transmission increases. here, we have explored the feasibility of using commercially available lamp kits, designed to detect the trypanozoon group of trypanosomes, as a xenomonitoring tool to screen tsetse flies for trypanosomes to be used in future epidemiological surveys. | 2016 | 26890882 |
| killing of trypanozoon parasites by the equine cathelicidin ecath1. | trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. control of nagana and surra depends to a great extent on chemotherapy. however, drug resistance to several of the front-line drugs is rising. furthermore, there is no official treatment for dourine. therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. host defense peptides have recently gained attention as promising candidates. we have pr ... | 2016 | 26824936 |
| orally active and selective tubulin inhibitors as anti-trypanosome agents. | there is an urgent need to develop a safe, effective, orally active, and inexpensive therapy for african trypanosomiasis due to the drawbacks of current drugs. selective tubulin inhibitors have the potential to be promising drug candidates for the treatment of this disease, which is based on the tubulin protein structural difference between mammalian and trypanosome cells. we propose to identify novel tubulin inhibitors from a compound library developed based on the lead compounds that selective ... | 2016 | 26771307 |
| trypanosome lytic factor-1 initiates oxidation-stimulated osmotic lysis of trypanosoma brucei brucei. | human innate immunity against the veterinary pathogen trypanosoma brucei brucei is conferred by trypanosome lytic factors (tlfs), against which human-infective t. brucei gambiense and t. brucei rhodesiense have evolved resistance. tlf-1 is a subclass of high density lipoprotein particles defined by two primate-specific apolipoproteins: the ion channel-forming toxin apol1 (apolipoprotein l1) and the hemoglobin (hb) scavenger hpr (haptoglobin-related protein). the role of oxidative stress in the t ... | 2016 | 26645690 |
| central nervous system parasitosis and neuroinflammation ameliorated by systemic il-10 administration in trypanosoma brucei-infected mice. | invasion of the central nervous system (cns) by african trypanosomes represents a critical step in the development of human african trypanosomiasis. in both clinical cases and experimental mouse infections it has been demonstrated that predisposition to cns invasion is associated with a type 1 systemic inflammatory response. using the trypanosoma brucei brucei gvr35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine il-10 lowers plasma ifn-γ ... | 2015 | 26505761 |
| structural and functional highlights of vacuolar soluble protein 1 from pathogen trypanosoma brucei brucei. | trypanosoma brucei (t. brucei) is responsible for the fatal human disease called african trypanosomiasis, or sleeping sickness. the causative parasite, trypanosoma, encodes soluble versions of inorganic pyrophosphatases (ppase), also called vacuolar soluble proteins (vsps), which are localized to its acidocalcisomes. the latter are acidic membrane-enclosed organelles rich in polyphosphate chains and divalent cations whose significance in these parasites remains unclear. we here report the crysta ... | 2015 | 26494625 |
| molecular characterization and classification of trypanosoma spp. venezuelan isolates based on microsatellite markers and kinetoplast maxicircle genes. | livestock trypanosomoses, caused by three species of the trypanozoon subgenus, trypanosoma brucei brucei, t. evansi and t. equiperdum is widely distributed throughout the world and constitutes an important limitation for the production of animal protein. t. evansi and t. equiperdum are morphologically indistinguishable parasites that evolved from a common ancestor but acquired important biological differences, including host range, mode of transmission, distribution, clinical symptoms and pathog ... | 2015 | 26467019 |
| discovery of indoline-2-carboxamide derivatives as a new class of brain-penetrant inhibitors of trypanosoma brucei. | there is an urgent need for new, brain penetrant small molecules that target the central nervous system second stage of human african trypanosomiasis (hat). we report that a series of novel indoline-2-carboxamides have been identified as inhibitors of trypanosoma brucei from screening of a focused protease library against trypanosoma brucei brucei in culture. we describe the optimization and characterization of this series. potent antiproliferative activity was observed. the series demonstrated ... | 2015 | 26418485 |
| combinations of alkaloids affecting different molecular targets with the saponin digitonin can synergistically enhance trypanocidal activity against trypanosoma brucei brucei. | the flagellate trypanosoma brucei causes sleeping sickness in humans and nagana in animals. only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. an underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. in this s ... | 2015 | 26349826 |
| a tegm6-4r antigen-based immunochromatographic test (ict) for animal trypanosomosis. | animal trypanosomosis is a disease that is distributed worldwide which results in huge economic losses due to reduced animal productivity. endemic regions are often located in the countryside where laboratory diagnosis is costly or inaccessible. the establishment of simple, effective, and accurate field tests is therefore of great interest to the farming and veterinary sectors. our study aimed to develop a simple, rapid, and sensitive immunochromatographic test (ict) for animal trypanosomosis ut ... | 2015 | 26290217 |
| novel ruthenium(ii) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites. | searching for new prospective antitrypanosomal agents, three novel ru(ii)-cyclopentadienyl compounds, [ru(η(5)-c5h5)(pph3)l], with hl=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. the compounds were evaluated in vitro on the blood circulating trypomastigote form of trypanosoma cruzi (dm28c strain), the infective form of trypanosoma brucei brucei (strain 427) and on j774 murine macrophages and human-derived ea.hy926 end ... | 2015 | 26275470 |
| 6-arylpyrazine-2-carboxamides: a new core for trypanosoma brucei inhibitors. | from a whole-organism high throughput screen of approximately 87000 compounds against trypanosoma brucei brucei, we recently identified eight new unique compounds for the treatment of human african trypanosomiasis. in an effort to understand the structure-activity relationships around these compounds, we report for the first time our results on a new class of trypanocides, the pyrazine carboxamides. attracted by the low molecular weight (270 g·mol(-1)) of our starting hit (9) and its potency (0. ... | 2015 | 26247439 |
| synthesis of biotinylated probes of artemisinin for affinity labeling. | in this data article, we described the synthetic routes to four biotinylated probes (2, 3, 4, and 5) of artemisinin and the associated experimental procedures. we also provided the physical data for the synthesized compounds. these synthesized biotinylated probes of artemisinin are useful molecular tools for the affinity-labeling study of target receptor proteins of artemisinin in tropical pathogens such as trypanosoma, leishmania, and schistosoma. the data provided herein are related to "biotin ... | 2015 | 26217765 |
| wild chimpanzees are infected by trypanosoma brucei. | although wild chimpanzees and other african great apes live in regions endemic for african sleeping sickness, very little is known about their trypanosome infections, mainly due to major difficulties in obtaining their blood samples. in present work, we established a diagnostic its1-based pcr assay that allows detection of the dna of all four trypanosoma brucei subspecies (trypanosoma brucei brucei, trypanosoma brucei rhodesiense, trypanosoma brucei gambiense, and trypanosoma brucei evansi) in f ... | 2015 | 26110113 |
| chemical constituents from waltheria indica exert in vitro activity against trypanosoma brucei and t. cruzi. | six extracts from the roots and the aerial parts of waltheria indica l. (malvaceae) were screened for their in vitro antitrypanosomal activity towards trypanosoma brucei brucei stib 427 strain, t. brucei rhodesiense stib 900 and trypanosoma cruzi tulahuen c4. the dichloromethane extract from the roots showed the highest activity against t. cruzi (ic50=0.74 μg/ml) as well as a good selectivity index (si value of 35). based on these results, this extract was fractionated and led to the isolation o ... | 2015 | 26072041 |
| trypanosoma evansi is alike to trypanosoma brucei brucei in the subcellular localisation of glycolytic enzymes. | trypanosoma evansi, which causes surra, is descended from trypanosoma brucei brucei, which causes nagana. although both parasites are presumed to be metabolically similar, insufficient knowledge of t. evansi precludes a full comparison. herein, we provide the first report on the subcellular localisation of the glycolytic enzymes in t. evansi, which is a alike to that of the bloodstream form (bsf) of t. b. brucei: (i) fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase (gapdh ... | 2015 | 26061149 |
| chimerization at the aqp2-aqp3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical trypanosoma brucei gambiense isolates. | aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in trypanosoma brucei brucei laboratory strains. recently, chimerization at the aqp2-aqp3 tandem locus was described from melarsoprol-pentamidine cross-resistant trypanosoma brucei gambiense isolates from sleeping sickness patients in the democratic republic of the congo. here, we demonstrate that reintroduction of wild-type aqp2 into one of these isolates fully restores drug susceptibility while expression of ... | 2015 | 26042196 |
| a pre-clinical animal model of trypanosoma brucei infection demonstrating cardiac dysfunction. | african trypanosomiasis (at), caused by trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias) in at remains largely unstudied. animal models of at demonstrating cardiac dysfunction similar to that described in field cases of at are critically required to trans ... | 2015 | 26023927 |
| localization of serum resistance-associated protein in trypanosoma brucei rhodesiense and transgenic trypanosoma brucei brucei. | african trypanosomes infect a broad range of mammals, but humans and some higher primates are protected by serum trypanosome lytic factors that contain apolipoprotein l1 (apol1). in the human-infective subspecies of trypanosoma brucei, trypanosoma brucei rhodesiense, a gene product derived from the variant surface glycoprotein gene family member, serum resistance-associated protein (sra protein), protects against apol1-mediated lysis. protection against trypanosome lytic factor requires the dire ... | 2015 | 25924022 |
| biotinylated probes of artemisinin with labeling affinity toward trypanosoma brucei brucei target proteins. | we studied the target proteins of artemisinin in trypanosoma brucei brucei using the affinity-labeling method. we designed and synthesized four biotinylated probes of artemisinin for use as molecular tools. their in vitro trypanocidal activities (data not shown) proved that they mimicked the biological action of artemisinin. we assessed the chemical stability for all of the probes in the parasite culture medium and lysate using reversed-phase high-performance liquid chromatography (hplc). after ... | 2015 | 25912417 |
| new heterocyclic compounds: synthesis and antitrypanosomal properties. | three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against trypanosoma brucei gambiense. in the quinoline series, the metallo antimalarial drug candidate (ferroquine, fq) and its ruthenium analogue (ruthenoquine, rq, compound 13) showed the highest in vitro activities with ic50 values around 0.1 μm. unfortunately, both compounds failed to cure trypanosoma brucei brucei infected mice in vivo. the other heterocyclic compounds were active ... | 2015 | 25835356 |
| human trypanolytic factor apol1 forms ph-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis. | apolipoprotein l-1 (apol1), the trypanolytic factor of human serum, can lyse several african trypanosome species including trypanosoma brucei brucei, but not the human-infective pathogens t. brucei rhodesiense and t. brucei gambiense, which are resistant to lysis by human serum. lysis follows the uptake of apol1 into acidic endosomes and is apparently caused by colloid-osmotic swelling due to an increased ion permeability of the plasma membrane. here we demonstrate that nanogram quantities of fu ... | 2015 | 25730870 |
| evaluation of histone deacetylase inhibitors (hdaci) as therapeutic leads for human african trypanosomiasis (hat). | two of the histone deacetylases, tbdac1 and tbdac3, have been reported to be essential genes in trypanosomes. therefore, we tested the activity of a panel of human histone deacetylase inhibitors (hdaci) for their ability to block proliferation of trypanosoma brucei brucei. among the hdaci's, the hydroxamic acid derivatives panobinostat and belinostat exhibited potency that appeared to make them viable candidates for development due to their reported pharmacokinetic characteristics. however, cell ... | 2015 | 25637120 |
| alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness. | human african trypanosomiasis or sleeping sickness is a severe, neglected tropical disease caused by the extracellular parasite trypanosoma brucei. the disease, which leads to chronic neuroinflammation, is characterized by sleep and wake disturbances, documented also in rodent models. in rats and mice infected with trypanosoma brucei brucei, we here tested the hypothesis that the disease could target neurons of the lateral hypothalamus (lh) containing orexin (ox)-a or melanin-concentrating hormo ... | 2015 | 25595977 |
| clastogenic effects of trypanosoma brucei brucei and trypanosoma evansi mixed infection in bone marrow of wistar rats. | the clastogenic effect of mixed infection of trypanosoma evansi and trypanosoma brucei brucei in the bone marrow (bm) cells of wistar albino rats was investigated. clastogenic effects were observed in the bm cells using the micronucleus assay. the findings indicate that t. evansi, t. b. brucei and mixed infection with both parasites induced the formation of micronucleated polychromatic erythrocyte (mn-pces) in the bm cells significantly (p < 0.05) by 60, 63 and 81 micronuclei/1000 pce respective ... | 2014 | 25458504 |
| a new nonpolar n-hydroxy imidazoline lead compound with improved activity in a murine model of late-stage trypanosoma brucei brucei infection is not cross-resistant with diamidines. | treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (bbb) to reach the parasites located in the brain. we report here the synthesis and evaluation of four new n-hydroxy and 12 new n-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. these compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological ph), were evaluated in vitro against trypanos ... | 2015 | 25421467 |
| structural basis for trypanosomal haem acquisition and susceptibility to the host innate immune system. | sleeping sickness is caused by trypanosome parasites, which infect humans and livestock in sub-saharan africa. haem is an important growth factor for the parasites and is acquired from the host by receptor-mediated uptake of haptoglobin (hp)-haemoglobin (hb) complexes. the parasite hp-hb receptor (hphbr) is also a target for a specialized innate immune defence executed by trypanosome-killing lipoprotein particles containing an hp-related protein in complex with hb. here we report the structure o ... | 2014 | 25410714 |
| application of crude and recombinant elisas and immunochromatographic test for serodiagnosis of animal trypanosomosis in the umkhanyakude district of kwazulu-natal province, south africa. | a total of 231 serum samples were collected from sheep (n=9), goats (n=99) and cattle (n=123) in northeastern kwazulu-natal, south africa. trypanosome infection was detected using trypanosoma brucei brucei crude antigen (tbbca) and t. congolense crude antigen (tcoca) elisa assays. recombinant antigen (t. evansi gm6 which consisted of 4 repeat domains, tegm6-4r) elisa and immunochromatographic test (ict) were also used. crude antigen elisa, tegm6-4r-elisa and ict detected 27.3%, 29% and 19.9% of ... | 2015 | 25342634 |
| a sensitive and reproducible in vivo imaging mouse model for evaluation of drugs against late-stage human african trypanosomiasis. | to optimize the trypanosoma brucei brucei gvr35 vsl-2 bioluminescent strain as an innovative drug evaluation model for late-stage human african trypanosomiasis. | 2015 | 25298516 |
| optical trapping reveals propulsion forces, power generation and motility efficiency of the unicellular parasites trypanosoma brucei brucei. | unicellular parasites have developed sophisticated swimming mechanisms to survive in a wide range of environments. cell motility of african trypanosomes, parasites responsible for fatal illness in humans and animals, is crucial both in the insect vector and the mammalian host. using millisecond-scale imaging in a microfluidics platform along with a custom made optical trap, we are able to confine single cells to study trypanosome motility. from the trapping characteristics of the cells, we deter ... | 2014 | 25269514 |
| the design and synthesis of potent and selective inhibitors of trypanosoma brucei glycogen synthase kinase 3 for the treatment of human african trypanosomiasis. | glycogen synthase kinase 3 (gsk3) is a genetically validated drug target for human african trypanosomiasis (hat), also called african sleeping sickness. we report the synthesis and biological evaluation of aminopyrazole derivatives as trypanosoma brucei gsk3 short inhibitors. low nanomolar inhibitors, which had high selectivity over the off-target human cdk2 and good selectivity over human gsk3β enzyme, have been prepared. these potent kinase inhibitors demonstrated low micromolar levels of inhi ... | 2014 | 25198388 |
| trypanosoma brucei brucei infected rats: micronucleated polychromatic erythrocytes. | the emergence of bone marrow micronucleated polychromatic erythrocytes (mn-pce) in rats experimentally infected with trypanosoma brucei brucei was examined in order to understand the bone marrow effects in trypanosomiasis infection. bone marrow was collected for micronucleus assay while blood samples were collected from infected rat for hematological analysis. the results showed evidence of mn-pce at 12.75 ± 0.65 micronuclei/ 1000 pce and 9.60 ± 2.95 micronuclei/1000 pce for rats infected for 21 ... | 2014 | 25134900 |
| increased trypanosoma brucei cathepsin-l activity inhibits human serum-mediated trypanolysis. | most african trypanosomes, including the veterinary species trypanosoma brucei brucei and t. congolense are susceptible to lysis by human serum. a recent study by alsford et al. [plos pathogens (2014) 10, e1004130] has identified a t. b. brucei lysosomal cathepsin with an inhibitory effect on human serum's trypanolytic action. | 2014 | 27441199 |
| effect of diminazene aceturate, levamisole and vitamin c combination therapy in rats experimentally infected with trypanosoma brucei brucei. | to investigate the effect of diminazene aceturate (da) alone or in combination with either levamisole and/or vitamin c in albino rats experimentally infected with trypanosoma brucei brucei. | 2014 | 25066391 |
| pyridyl benzamides as a novel class of potent inhibitors for the kinetoplastid trypanosoma brucei. | a whole-organism screen of approximately 87000 compounds against trypanosoma brucei brucei identified a number of promising compounds for medicinal chemistry optimization. one of these classes of compounds we termed the pyridyl benzamides. while the initial hit had an ic50 of 12 μm, it was small enough to be attractive for further optimization, and we utilized three parallel approaches to develop the structure-activity relationships. we determined that the physicochemical properties for this cla ... | 2014 | 24978605 |
| 9- and 11-substituted 4-azapaullones are potent and selective inhibitors of african trypanosoma. | trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-saharan africa and causative agents of severe diseases in humans and livestock. in order to identify new antitrypanosomal chemotypes against african trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a heck reaction as key step. among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal ac ... | 2014 | 24973661 |
| the susceptibility of trypanosoma congolense and trypanosoma brucei to isometamidium chloride and its synthetic impurities. | since the 1950s, the chemotherapy of animal african trypanosomosis in cattle has essentially relied on only two compounds: isometamidium chloride (ism), a phenanthridine, and diminazene aceturate, an aromatic diamidine. the commercial formulations of ism, including veridium(®) and samorin(®), are a mixture of different compounds: ism is the major component, mixed with the red isomer, blue isomer and disubstituted compound. to investigate the pharmacological effects of these individual compounds ... | 2014 | 24836423 |
| cathepsin-l can resist lysis by human serum in trypanosoma brucei brucei. | closely related african trypanosomes cause lethal diseases but display distinct host ranges. specifically, trypanosoma brucei brucei causes nagana in livestock but fails to infect humans, while trypanosoma brucei gambiense and trypanosoma brucei rhodesiense cause sleeping sickness in humans. t. b. brucei fails to infect humans because it is sensitive to innate immune complexes found in normal human serum known as trypanolytic factor (tlf) 1 and 2; the lytic component is apolipoprotein-l1 in both ... | 2014 | 24830321 |
| antitrypanosomal activity & docking studies of components of crateva adansonii dc leaves: novel multifunctional scaffolds. | chemical investigation of crateva adansonii dc has led to the isolation of aurantiamide acetate, a novel ethyl pyropheophorbide a, purpurin-18 ethyl ester and pyropheophorbide a. their structures were elucidated using extensive spectral data. these metabolites were then evaluated for their in vitro bioactivity against the african trypanosome trypanosoma brucei brucei (s427) blood stream forms. anti-trypanosomal activity decreased with aurantiamide acetate (mic 25µm), while it increased with the ... | 2014 | 24660686 |
| antitrypanosomal activity & docking studies of isolated constituents from the lichen cetraria islandica: possibly multifunctional scaffolds. | chemical investigation of the lichen cetraria islandica has led to the isolation of four compounds identified as protolichesterinic acid, lichesterinic acid, protocetraric acid and fumarprotocetraric acid. their structures were characterized using their physical and spectroscopic data. using an alamarblue™ 96 well microplate assay, these compounds were tested to evaluate their trypanocidal activity against trypanosoma brucei brucei. protolichesterinic acid (mic = 6.30 µm) and lichesterinic acid ... | 2014 | 24660683 |
| phytochemical and antitrypanosomal investigation of the fractions and compounds isolated from artemisia elegantissima. | trypanosoma brucei brucei (t.b. brucei) infection causes death in cattle, while the current treatments have serious toxicity problems. however, natural products can be used to overcome the problems associated with parasitic diseases including t.b. brucei. | 2014 | 24597622 |
| isothiocoumarin-3-carboxylic acid derivatives: synthesis, anticancer and antitrypanosomal activity evaluation. | a series of new isothiocoumarin-3-carboxylic acids derivatives had been obtained based on the 5-arylidenerhodanines hydrolysis. anticancer activity screening allowed identification of 7,8-dimethoxy-1-oxo-1h-isothiochromene-3-carboxylic acid (4-phenylthiazol-2-yl)-amide (30) with the highest level of antimitotic activity (gi50nci-h322m/nsc lung cancer = 1.28 μm). evaluation of the antitrypanosomal activity against trypanosoma brucei brucei showed that investigated compounds did not exhibit signif ... | 2014 | 24530491 |
| n¹,n¹-dimethyl-n³-(3-(trifluoromethyl)phenethyl)propane-1,3-diamine, a new lead for the treatment of human african trypanosomiasis. | the natural product, convolutamine i (1), has anti-trypanosomal activity however it has a high molecular weight of 473 due to a presence of 3 bromine atoms. the synthesis of the natural product convolutamine i (1) together with its analogues are presented. a sar study against trypanosoma brucei brucei led to compounds with improved physico-chemical properties: lower molecular weight and lower log p while maintaining potency (with a slight 2-fold improvement). | 2014 | 24530464 |
| erythrina abyssinica prevents meningoencephalitis in chronic trypanosoma brucei brucei mouse model. | human african trypanosomiasis is prevalent in sub-sahara african countries that lie between 14° north and 29° south of the equator. sixty million people are at risk of infection. trypanosoma brucei gambesience occurs in west and central africa while trypanosoma brucei rhodesience occurs in east and southern africa. the neurological stage of the disease is characterized by neuroinflammation. about 10% of patients treated with the recommended drug, melarsoprol develop post treatment reactive encep ... | 2014 | 24452611 |
| determination of the prevalence of african trypanosome species in indigenous dogs of mambwe district, eastern zambia, by loop-mediated isothermal amplification. | dogs have been implicated to serve as links for parasite exchange between livestock and humans and remain an important source of emerging and re-emerging diseases including trypanosome infections. yet, canine african trypanosomosis (cat), particularly in indigenous dogs (mongrel breed) remains under- reported in literature. this study evaluated the performance of loop-mediated isothermal amplification (lamp) in detecting trypanosomes in blood from indigenous dogs of tsetse-infested mambwe distri ... | 2014 | 24411022 |
| trypanocidal and cytotoxic evaluation of synthesized thiosemicarbazones as potential drug leads against sleeping sickness. | thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. the wide range of their biological activities depends generally on their related aldehyde or ketone groups. here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. benzophenone and derivatives were used with n(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1-5). their struc ... | 2014 | 24407605 |
| semisynthesis of salviandulin e analogues and their antitrypanosomal activity. | a series of analogues of salviandulin e, a rearranged neoclerodane diterpene originally isolated from salvia leucantha (lamiaceae), were prepared and their in vitro activity against trypanosoma brucei brucei was evaluated with currently used therapeutic drugs as positive controls. one of the 19 compounds prepared and assayed in the present study, butanoyl 3,4-dihydrosalviandulin e analogue was found to be a possible candidate for an antitrypanosomal drug with fairly strong antitrypanosomal activ ... | 2014 | 24388808 |
| flavonoid mixture ameliorates increase in erythrocyte osmotic fragility and malondialdehyde concentration induced by trypanosoma brucei brucei-infection in wistar rats. | the experiment was performed with the aim of investigating the effect of a flavonoid mixture, daflon® 500 mg (df) on the erythrocyte fragility and lipoperoxidative changes, induced by trypanosoma brucei brucei infection in wistar rats. fifty adult male rats randomly divided into five groups of 10 animals each were used. rats in the control group were administered (1 ml/kg) distilled water only, while the other groups were infected with t. brucei brucei and treated with daflon® 500 mg and/or dimi ... | 2014 | 24332272 |
| evaluation of antitrypanosomal and anti inflammatory activities of selected nigerian medicinal plants in mice. | the extracts of nine selected nigerian medicinal plants were investigated on trypanosoma brucei brucei infected mice. the anti-inflammatory properties of hexane fraction of the most promising u. chamae extract was assessed by acute oedema of the mice paw model while the modulatory effect of the extract on delayed-type hypersensitivity (dth) response on in vivo leucocytes mobilization was evaluated. 'dose-probing acute toxicity tests' established an oral and intraperitoneal ld50 for t. ivorensis ... | 2013 | 24311871 |
| trypanocidal activity of marine natural products. | marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. this has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human african trypanosomiasis and chagas disease, for which very few drugs are currently available. this article will review the marine natural products for which activity against the kinetoplastid parasites; trypanosoma brucei brucei, t.b. rhodesiens ... | 2013 | 24152565 |
| in vitro antitrypanosomal activity of the cyclodepsipeptides, cardinalisamides a-c, from the insect pathogenic fungus cordyceps cardinalis nbrc 103832. | during the search for new antitrypanosomal drug leads, three new antitrypanosomal compounds, cardinalisamides a-c (1-3), were isolated from cultures of the insect pathogenic fungus cordyceps cardinalis nbrc 103832. their structures were elucidated using ms analyses and extensive 2d-heteronuclear nmr. the absolute configurations of 1-3 were addressed by chemical degradation and marfey's analysis. 1-3 showed in vitro antitrypanosomal activity against trypanosoma brucei brucei with ic50 values of 8 ... | 2014 | 24084682 |
| in vivo imaging of trypanosome-brain interactions and development of a rapid screening test for drugs against cns stage trypanosomiasis. | human african trypanosomiasis (hat) manifests in two stages of disease: firstly, haemolymphatic, and secondly, an encephalitic phase involving the central nervous system (cns). new drugs to treat the second-stage disease are urgently needed, yet testing of novel drug candidates is a slow process because the established animal model relies on detecting parasitemia in the blood as late as 180 days after treatment. to expedite compound screening, we have modified the gvr35 strain of trypanosoma bru ... | 2013 | 23991236 |
| a longitudinal survey of african animal trypanosomiasis in domestic cattle on the jos plateau, nigeria: prevalence, distribution and risk factors. | trypanosomiasis is a widespread disease of livestock in nigeria and a major constraint to the rural economy. the jos plateau, nigeria was free from tsetse flies and the trypanosomes they transmit due to its high altitude and the absence of animal trypanosomiasis attracted large numbers of cattle-keeping pastoralists to inhabit the plateau. the jos plateau now plays a significant role in the national cattle industry, accommodating approximately 7% of the national herd and supporting 300,000 pasto ... | 2013 | 23958205 |
| vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: design, synthesis, biological and computational evaluation. | a series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against trypanosoma brucei brucei . these electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, tbcatb and rhodesain, through alkylation of a key cysteine residue within the protease active site. the series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to ... | 2013 | 23952916 |
| identification of coding sequences from a freshly prepared trypanosoma brucei brucei expression library by polymerase chain reaction. | animal african trypanosomiasis (aat) also known as nagana is a devastating disease among domestic animals in large parts of sub-saharan africa causing loses in milk and meat production as well as traction power. however, there is currently no commercial vaccine against aat. the parasites have also developed resistance to some of the drugs in use. moreover, the use of affordable computer-aided wet bench methods in the search for vaccine and/or new drug targets against this disease have not yet be ... | 2013 | 23936738 |
| effects of dietary selenium supplementation on parasitemia, anemia and serum proteins of trypanosoma brucei brucei infected rats. | trypanosomosis has been associated with immunosuppression, anemia and oxidative damage while selenium possesses both immunostimulatory and antioxidative effects. this study was designed to assess the effect of dietary selenium supplementation on parasitemia, anemia, survival pattern and serum protein profiles of trypanosome-infected rats. twenty five rats, divided into five groups (a-e) of 5 each, were treated as follows: 4, 8 and 16 ppm (ppm) of selenium in their feed, respectively throughout t ... | 2013 | 23916765 |
| anti-trypanosomal effect of peristrophe bicalyculata extract on trypanosoma brucei brucei-infected rats. | to investigate the in vitro and in vivo effect of whole plant extracts of peristrophe bicalyculata on trypanosoma brucei brucei-infected rats. | 2013 | 23835905 |
| comparative diagnostic and analytical performance of pcr and lamp-based trypanosome detection methods estimated using pooled whole tsetse flies and midguts. | detection of trypanosomes that cause disease in human beings and livestock within their tsetse fly hosts is an essential component of vector and disease control programmes. several molecular-based diagnostic tests have been developed for this purpose. many of these tests, while sensitive, require analysis of trypanosome dna extracted from single flies, or from pooled tsetse fly heads and amplified trypanosome dna. in this study, we evaluated the relative analytical and diagnostic sensitivities o ... | 2013 | 23796572 |
| chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from cymbopogon nardus l. | essential oil from cymbopogon nardus was evaluated for activity against trypanosoma brucei brucei bs221 (ic50 = 0.31 ± 0.03 μg/ml) and cytotoxic effect on normal kidney (vero) cells (ic50 = >100 μg/ml). the crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; f4 (ic50 = 0.61 ± 0.06 μg/ml), f6 (ic50= 0.73 ± 0.33 μg/ml), f7 (ic50 = 1.15 ± 0 μg/ml) and f8 (ic50 = 1.11 ± 0.01 μg/ml). these active fractions did not exhibi ... | 2013 | 23665703 |
| phenolics-rich fraction of khaya senegalensis stem bark: antitrypanosomal activity and amelioration of some parasite-induced pathological changes. | the stem bark of khaya senegalensis a. juss (meliaceae) is currently used for the treatment of trypanosomiasis by traditional practitioners in nigeria. | 2013 | 23627467 |
| magnitude and origin of the enhanced basicity of the catalytic glutamate of triosephosphate isomerase. | glu-167 of triosephosphate isomerase from trypanosoma brucei brucei (tbbtim) acts as the base to deprotonate substrate to form an enediolate phosphate trianion intermediate. we report that there is a large ~6 pk unit increase in the basicity of the carboxylate side chain of glu-167 upon binding of the inhibitor phosphoglycolate trianion (i(3-)), an analog of the enediolate phosphate intermediate, from pkeh ≈ 4 for the protonated free enzyme eh to pk(ehi) ≈ 10 for the protonated enzyme-inhibitor ... | 2013 | 23560625 |
| whole-organism high-throughput screening against trypanosoma brucei brucei. | human african trypanosomiasis (hat) occurs as a result of infection with the protozoan parasites trypanosoma brucei gambiense and t.b. rhodesiense and is nearly always fatal without treatment. however, current therapeutic options are severely limited and there is a desperate need for new compounds to treat the disease. whole-cell high-throughput screening (hts) is a technique frequently used to identify compounds with trypanocidal activity. | 2013 | 23540598 |
| pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms. | african trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite. | 2013 | 23505454 |
| lactone-rich fraction from vernonia blumeoides: antitrypanosomal activity and alleviation of the parasite-induced anemia and organ damage. | the anti-trypanosoma brucei brucei activity in vitro and in vivo of a lactone-rich fraction of vernonia blumeoides leaves (vblf) and its potential in alleviating trypanosome-induced anemia and organ damage were investigated. gas chromatography-mass spectrometry (gc-ms) analysis of vblf revealed the presence of a number of lactone-containing compounds. in an in vitro study, vblf showed concentration-dependent activity and was further used to treat t. brucei brucei-infected rats. the vblf treatmen ... | 2013 | 23292278 |
| iron-sulfur cluster binding by mitochondrial monothiol glutaredoxin-1 of trypanosoma brucei: molecular basis of iron-sulfur cluster coordination and relevance for parasite infectivity. | monothiol glutaredoxins (1-c-grxs) are small proteins linked to the cellular iron and redox metabolism. trypanosoma brucei brucei, model organism for human african trypanosomiasis, expresses three 1-c-grxs. 1-c-grx1 is a highly abundant mitochondrial protein capable to bind an iron-sulfur cluster (isc) in vitro using glutathione (gsh) as cofactor. we here report on the functional and structural analysis of 1-c-grx1 in relation to its isc-binding properties. | 2013 | 23259530 |
| in vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human african trypanosomiasis. | new drugs for the treatment of human african trypanosomiasis are urgently needed. a number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for trypanosoma brucei subsp. brucei viability. described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. specifically, 6-([6-fluoro-3,4-dihydro-2h-1-benzopyran-4-yl)]oxy)-n-(piperidin-4-yl)pyrazin-2-amine (c ... | 2013 | 23254423 |
| identification of compounds with anti-proliferative activity against trypanosoma brucei brucei strain 427 by a whole cell viability based hts campaign. | human african trypanosomiasis (hat) is caused by two trypanosome sub-species, trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. drugs available for the treatment of hat have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. hence, there is considerable need to find new alternative and less toxic drugs. an approach to identify starting points for new drug candidates is high throughput screening (hts) of large comp ... | 2012 | 23209849 |
| application of a resazurin-based high-throughput screening assay for the identification and progression of new treatments for human african trypanosomiasis. | human african trypanosomiasis (hat) is caused by the protozoan parasite trypanosoma brucei, and the disease is fatal if untreated. there is an urgent need to develop new, safe and effective treatments for hat because current drugs have extremely poor safety profiles and are difficult to administer. here we report the development and application of a cell-based resazurin reduction assay for high throughput screening and identification of new inhibitors of t. b. brucei as starting points for the d ... | 2012 | 24533287 |
| effects of the green tea catechin (-)-epigallocatechin gallate on trypanosoma brucei. | the current pharmacopeia to treat the lethal human and animal diseases caused by the protozoan parasite trypanosoma brucei remains limited. the parasite's ability to undergo antigenic variation represents a considerable barrier to vaccine development, making the identification of new drug targets extremely important. recent studies have demonstrated that fatty acid synthesis is important for growth and virulence of trypanosoma brucei brucei, suggesting this pathway may have therapeutic potential ... | 2012 | 24533284 |
| pyrimidine salvage in trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines. | african trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. however, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. detailed characterization of pyrimidine transport activities in bloodstream form trypanosoma brucei brucei found that these cells express a high-affinity uracil transpo ... | 2013 | 23188714 |
| effect of ivermectin on trypanosoma brucei brucei in experimentally infected mice. | human and livestock african trypanosomiasis, otherwise known as sleeping sickness, is a neglected tropical disease of public health importance in west and central africa. in view of the adverse side effects of the antitrypanosomal drugs, the relatively few side effects observed in ivermectin use, and because both onchocerciasis and typanosomiasis occur in overlapping foci in africa, it would be desirable if the ivermectin that has been used successfully on onchocerciasis management could also be ... | 2012 | 23135008 |
| synthesis and antitrypanosomal activity of new 6,6,7-trisubstituted thiopyrano[2,3-d][1,3]thiazoles. | а series of novel 6,6,7-trisubstituted thiopyrano[2,3-d][1,3]thiazoles-based molecules have been synthesized and evaluated as potential antitrypanosomal agents. the most active analogue 3b inhibited trypanosoma brucei brucei and trypanosoma brucei gambiense with an ic(50) of 0.26 and 0.42 μм, respectively. they could be considered as potent hits for further antitrypanosomal drug discovery efforts. | 2012 | 23084895 |
| biochemical and morphological changes in trypanosoma brucei brucei-infected rats treated with homidium chloride and diminazene aceturate. | chemotherapy which is one of the major methods for controlling trypanosomal infections is beset with several challenges including unwanted toxicity and limited efficacy. these factors and others underscore research efforts aimed at finding safer and more effective therapeutic agents for trypanosomiasis. homidium chloride and diminazene aceturate are registered drugs for the treatment of animal trypanosomiasis. | 2012 | 23072845 |