| antitrypanosomal and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives. | cryptolepine derivatives containing alkyldiamine side-chains, 2, with potent inhibitory activity against trypanosoma brucei brucei are reported. compounds 2 showed improved activity and selectivity to t. b. brucei when compared to the lead compound. the most selective compound, 2k, presents a selectivity index value of 6200 and an ic(50) of 10nm against the parasite. these derivatives are also potent inhibitors of the trypanosome papain-like cysteine proteases cruzain, which could, at least in p ... | 2012 | 22926067 |
| comparative serum biochemical changes in mongrel dogs following single and mixed infections of trypanosoma congolense and trypanosoma brucei brucei. | the serum activities of alkaline phosphatase (ap), alanine aminotransferase (alt), aspartate aminotransferase (ast) and the serum levels of conjugated bilirubin (cb), blood urea nitrogen (bun) and creatinine were studied following single and mixed infections of mongrel dogs with trypanosoma congolense and trypanosoma brucei brucei. twenty mongrel dogs of both sexes aged between 3 and 6 months, and weighing between 2.5 and 5.9 kg were used for the study. the dogs were kept in clean metal cages in ... | 2012 | 22694831 |
| iotrochamides a and b, antitrypanosomal compounds from the australian marine sponge iotrochota sp. | bioassay-guided isolation of the ch(2)cl(2)/meoh extract from the australian sponge iotrochota sp. resulted in the purification of two new n-cinnamoyl-amino acids, iotrochamides a (1) and b (2). the chemical structures of 1 and 2 were determined by 1d/2d nmr and ms data analyses. compounds 1 and 2 were shown to inhibit trypanosoma brucei brucei with ic(50) values of 3.4 and 4.7 μm, respectively. | 2012 | 22677313 |
| mechanism for activation of triosephosphate isomerase by phosphite dianion: the role of a hydrophobic clamp. | the role of the hydrophobic side chains of ile-172 and leu-232 in catalysis of the reversible isomerization of r-glyceraldehyde 3-phosphate (gap) to dihydroxyacetone phosphate (dhap) by triosephosphate isomerase (tim) from trypanosoma brucei brucei (tbb) has been investigated. the i172a and l232a mutations result in 100- and 6-fold decreases in k(cat)/k(m) for the isomerization reaction, respectively. the effect of the mutations on the product distributions for the catalyzed reactions of gap and ... | 2012 | 22583393 |
| the origins of the trypanosome genome strains trypanosoma brucei brucei treu 927, t. b. gambiense dal 972, t. vivax y486 and t. congolense il3000. | the genomes of several tsetse-transmitted african trypanosomes (trypanosoma brucei brucei, t. b. gambiense, t. vivax, t. congolense) have been sequenced and are available to search online. the trypanosome strains chosen for the genome sequencing projects were selected because they had been well characterised in the laboratory, but all were isolated several decades ago. the purpose of this short review is to provide some background information on the origins and biological characterisation of the ... | 2012 | 22483376 |
| antitrypanosomal properties of panax ginseng c. a. meyer: new possibilities for a remarkable traditional drug. | african trypanosomiasis is still a major health problem in many sub-saharan countries in africa. we investigated the effects of three preparations of panax ginseng, panax notoginseng, isolated ginsenosides, and the polyacetylene panaxynol on trypanosoma brucei brucei and the human cancer cell line hela. hexane extracts and the pure panaxynol were toxic and at the same time highly selective against t. b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic ... | 2013 | 22473703 |
| haptoglobin-hemoglobin receptor independent killing of african trypanosomes by human serum and trypanosome lytic factors. | the haptoglobin-hemoglobin receptor (hphbr) of african trypanosomes plays a critical role in human innate immunity against these parasites. localized to the flagellar pocket of the veterinary pathogen trypanosoma brucei brucei this receptor binds trypanosome lytic factor-1 (tlf-1), a subclass of human high-density lipoprotein (hdl) facilitating endocytosis, lysosomal trafficking and subsequent killing. recently, we found that group 1 trypanosoma brucei gambiense does not express a functional hph ... | 2016 | 22286709 |
| bioactive diterpenes and sesquiterpenes from the rhizomes of wild ginger (siphonochilus aethiopicus (schweinf) b.l burtt). | wild ginger (siphonochilus aethiopicus (schweinf) b.l burtt) is used in traditional medicines in the west and south of africa. in the present study, the crude hexane extract of wild ginger was evaluated for in vitro bioactivity. the components isolated from the plant for the first time are: epi-curzerenone, furanodienone (sesquiterpenes), 8(17),12e-labdadiene-15,16-dial, 15-hydroxy-8(17),12e-labdadiene-16-al and 16-oxo-8(17),12e-labdadiene-15-oic acid (labdanes). cytotoxicity determinations usin ... | 2012 | 23983325 |
| cis editing in trypanosoma brucei brucei as a model for understanding guide-rna structural and functional requirements. | | 2004 | 27690603 |
| oral administration of azithromycin ameliorates trypanosomosis in trypanosoma congolense-infected mice. | animal trypanosomosis is a devastating parasitic disease that is of economic importance to livestock production. the infection includes animal african trypanosomosis, surra, and dourine. the treatment is based solely on few compounds that were discovered decades ago and which are associated with severe toxicity. furthermore, it is likely that the parasite has developed resistance towards them. thus, there is an urgent need for new, accessible, and less toxic drugs. azithromycin is an antibiotic ... | 2017 | 28674747 |
| genome-wide snp analysis reveals distinct origins of trypanosoma evansi and trypanosoma equiperdum. | trypanosomes cause a variety of diseases in man and domestic animals in africa, latin america and asia. in the trypanozoon subgenus, trypanosoma brucei gambiense and t. b. rhodesiense cause human african trypanosomiasis, while t. b. brucei, t. evansi and t. equiperdum are responsible for nagana, surra and dourine in domestic animals, respectively. the genetic relationships between t. evansi and t. equiperdum and other trypanozoon species remain unclear because the majority of phylogenetic analys ... | 2017 | 28541535 |
| trypanosoma infection favors brucella elimination via il-12/ifnγ-dependent pathways. | this study develops an original co-infection model in mice using brucella melitensis, the most frequent cause of human brucellosis, and trypanosoma brucei, the agent of african trypanosomiasis. although the immunosuppressive effects of t. brucei in natural hosts and mice models are well established, we observed that the injection of t. brucei in mice chronically infected with b. melitensis induces a drastic reduction in the number of b. melitensis in the spleen, the main reservoir of the infecti ... | 2017 | 28824630 |
| expression, purification, and crystallization of type 1 isocitrate dehydrogenase from trypanosoma brucei brucei. | isocitrate dehydrogenases (idhs) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. depending on the electron acceptor and subcellular localization, these enzymes are classified as nadp(+)-dependent idh1 in the cytosol or peroxisomes, nadp(+)-dependent idh2 and nad(+)-dependent idh3 in mitochondria. trypanosoma brucei is a protozoan parasite that causes african sleeping sickness in humans and nagana disease in animals. here, for the first time, a ... | 2017 | 28642005 |
| development of novel peptide-based michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (ntds). | this paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. the inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of trypanosoma brucei rhodesiense and falcipain-2 of plasmodium falciparum. we exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. the michael acceptors inhibited both rhodesain an ... | 2017 | 28763614 |
| rodent-free cyclical transmission of trypanosoma brucei brucei. | we provide a simple protocol enabling cyclical transmission of trypanosoma brucei brucei to be performed without the need for mammals. these procedures have two advantages: they are in line with 3r principles of animal use - replace, refine, reduce - and may enable more laboratories to study the complete life cycle. | 2017 | 28843782 |
| expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental african trypanosomiasis. | human african trypanosomiasis or sleeping sickness, caused by the parasite trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. the relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. this study investigates the expression of interferon (ifn)-γ and ifn-inducible chemokine genes in the brain, and the levels of cxcl10 in the serum and cerebrospinal fluid prior to a ... | 2017 | 28821016 |
| synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosomal agents. | african trypanosomiasis is still a threat to human health due to the severe side-effects of current drugs. we identified selective tubulin inhibitors that showed the promise to the treatment of this disease, which was based on the tubulin protein structural difference between mammalian and trypanosome cells. further lead optimization was performed in the current study to improve the efficiency of the drug candidates. we used trypanosoma brucei brucei cells as the parasite model, and human normal ... | 2017 | 28428042 |
| a new chimeric triple reporter fusion protein as a tool for in vitro and in vivo multimodal imaging to monitor the development of african trypanosomes and leishmania parasites. | trypanosomiases and leishmaniases, caused by a group of related protist parasites, are neglected tropical diseases currently threatening >500 million people worldwide. reporter proteins have revolutionised the research on infectious diseases and have opened up new advances in the understanding of trypanosomatid-borne diseases in terms of both biology, pathogenesis and drug development. here, we describe the generation and some applications of a new chimeric triple reporter fusion protein combini ... | 2018 | 29339220 |
| design, synthesis, and antiprotozoal evaluation of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives. | a series of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives was synthesized, and the compounds were screened in vitro against three protozoan parasites (plasmodium falciparum, leishmania donovani, and trypanosoma brucei brucei). biological results showed antiparasitic activity with ic50 values in the μm range. the in vitro cytotoxicity of these molecules was assessed by incubation with human hepg2 cells; for some derivatives, cytotoxicity was observed at significantl ... | 2017 | 29266861 |
| tsetse fly (glossina pallidipes) midgut responses to trypanosoma brucei challenge. | tsetse flies (glossina spp.) are the prominent vector of african trypanosome parasites (trypanosoma spp.) in sub-saharan africa, and glossina pallidipes is the most widely distributed species in kenya. this species displays strong resistance to infection by parasites, which are typically eliminated in the midgut shortly after acquisition from the mammalian host. although extensive molecular information on immunity for the related species glossina morsitans morsitans exists, similar information i ... | 2017 | 29258576 |
| antimicrobial and antiparasitic activities of three algae from the northwest coast of algeria. | the objective of this study was to investigate the biological activities of algerian algae, sargassum vulgare, cladostephus hirsutus and rissoella verruculosa. antimicrobial activity of the crude extracts and their fractions was assessed using the disc diffusion assay, the minimum inhibitory concentration and the minimum bactericidal concentration. antiparasitic activity was studied in vitro against the blood stream forms of trypanosoma brucei brucei and the intraerythrocytic stages of plasmodiu ... | 2017 | 29166772 |
| intracellular diminazene aceturate content and adenosine incorporation in diminazene aceturate-resistant babesia gibsoni isolate in vitro. | the mechanism of the development of diminazene aceturate (da) resistance in babesia gibsoni is still unknown even though da-resistant b. gibsoni isolate was previously developed in vitro. to clarify the mechanisms of da-resistance in b. gibsoni, we initially examined the intracellular da content in the da-resistant isolate using high-performance liquid chromatography, and compared it with that in the wild-type. as a result, the intracellular da content in the da-resistant isolate was significant ... | 2017 | 29122576 |
| apol1 nephrotoxicity: what does ion transport have to do with it? | apolipoprotein l1 (apol1) protein is the human serum factor that protect human beings against trypanosoma brucei brucei, the cause of trypanosomiasis. subspecies of t b brucei that cause human sleeping sickness-t b gambiense and t b rhodesiense evolved molecular mechanisms that enabled them to evade killing by apol1. sequence changes (termed g1 and g2) in the apol1 gene that restored its ability to kill t b rhodesiense also increase the risk of developing glomerular diseases and accelerate progr ... | 2017 | 29110762 |
| improving anti-trypanosomal activity of alkamides isolated from achillea fragrantissima. | in previous studies the aerial parts of achillea fragrantissima were found to have substantial antileishmanial and antitrypanosomal activity. a bioassay-guided fractionation of a dichloromethane extract yielded the isolation of the essential anti-trypanosomal compounds of the plant. seven sesquiterpene lactones (including achillolide-a), two flavonoids, chrysosplenol-d and chrysosplenetine, and four alkamides (including pellitorine) were identified. this is the first report for the isolation of ... | 2017 | 29108932 |
| biological and phytochemical investigations on caesalpinia benthamiana, a plant traditionally used as antimalarial in guinea. | caesalpinia benthamiana is widely used as antimalarial in guinean traditional medicine. leaf extracts of the plant were tested for their in vitro antiprotozoal activity against trypanosoma brucei brucei and t. cruzi and the chloroquine-sensitive ghana strain of plasmodium falciparum along with their cytotoxicity on mrc-5 cells. the methanolic extract showed the strongest antiprotozoal activity against p. falciparum (ic50 4 μg/ml), a good activity against t. brucei (ic50 13 μg/ml), and a moderate ... | 2017 | 29081823 |
| screening a natural product-based library against kinetoplastid parasites. | kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human african trypanosomiasis (hat) and chagas disease. these neglected tropical diseases (ntds) impact on some of the world's lowest socioeconomic communities. current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. in this study, the davis open access natural product-based library was screened against kinetoplastids (leishmania ... | 2017 | 29023425 |
| apols with low ph dependence can kill all african trypanosomes. | the primate-specific serum protein apolipoprotein l1 (apol1) is the only secreted member of a family of cell death promoting proteins 1-4 . apol1 kills the bloodstream parasite trypanosoma brucei brucei, but not the human sleeping sickness agents t.b. rhodesiense and t.b. gambiense 3 . we considered the possibility that intracellular members of the apol1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic t. brucei subspecies. here we show th ... | 2017 | 28924146 |