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the use of loop-mediated isothermal amplification (lamp) to detect the re-emerging human african trypanosomiasis (hat) in the luangwa and zambezi valleys.loop-mediated isothermal amplification (lamp) is a novel strategy which amplifies dna with high sensitivity and rapidity under isothermal conditions. in the present study, the performance of the repetitive insertion mobile element (rime)-lamp and human serum resistance-associated gene (sra)-lamp assays were evaluated using clinical specimens obtained from four male patients from luangwa and zambezi valleys in zambia and zimbabwe, respectively.201223211002
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 ...201223209849
an exploratory gis-based method to identify and characterise landscapes with an elevated epidemiological risk of rhodesian human african trypanosomiasis.specific land cover types and activities have been correlated with trypanosoma brucei rhodesiense distributions, indicating the importance of landscape for epidemiological risk. however, methods proposed to identify specific areas with elevated epidemiological risk (i.e. where transmission is more likely to occur) tend to be costly and time consuming. this paper proposes an exploratory spatial analysis using geo-referenced human african trypanosomiasis (hat) cases and matched controls from serer ...201223171150
stage progression and neurological symptoms in trypanosoma brucei rhodesiense sleeping sickness: role of the cns inflammatory response.human african trypanosomiasis progresses from an early (hemolymphatic) stage, through cns invasion to the late (meningoencephalitic) stage. in experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in african trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance.201223145191
trypanosome resistance to human innate immunity: targeting achilles' heel.trypanosome lytic factors (tlfs) are powerful, naturally occurring toxins in humans that provide sterile protection against infection by several african trypanosomes. these trypanocidal complexes predominantly enter the parasite by binding to the trypanosome haptoglobin/hemoglobin receptor (hphbr), trafficking to the lysosome, causing membrane damage and, ultimately, cell lysis. despite tlf-mediated immunity, the parasites that cause human african trypanosomiasis (hat), trypanosoma brucei rhodes ...201223059119
molecular epidemiological studies on animal trypanosomiases in ghana.african trypanosomes are extracellular protozoan parasites that are transmitted between mammalian hosts by the bite of an infected tsetse fly. human african trypanosomiasis (hat) or sleeping sickness is caused by trypanosoma brucei rhodesiense or t. brucei gambiense, while african animal trypanosomiasis (aat) is caused mainly by t. vivax, t. congolense, t. simiae,t. evansi and t. brucei brucei. trypanosomiasis is of public health importance in humans and is also the major constraint for livestoc ...201223025330
human african trypanosomiasis in a traveler: diagnostic pitfalls.abstract. an israeli traveler returning from tanzania presented with a relapsing febrile illness. a diagnosis of trypanosoma brucei rhodesiense infection was established by blood smear after nearly a month. blood polymerase chain reaction failed to provide an early diagnosis of human african trypanososmiasis. recognition of suggestive signs should prompt physicians to perform repeated tests before ruling out human african trypanososmiasis.201222855756
pharmacology of db844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human african trypanosomiasis.novel drugs to treat human african trypanosomiasis (hat) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (nect) to who model lists of essential medicines against second stage hat, where parasites have invaded the central nervous system (cns). the pharmacology of a potential orally available lead compound, n-methoxy-6-{5-[4-(n-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (db844), was evaluated in a vervet monkey model of second stage hat, ...201222848769
cinnamoylphenethyl amides from polygonum hyrcanicum possess anti-trypanosomal activity.a methanolic extract from aerial parts of polygonum hyrcanicum (polygonaceae) showed high activity against trypanosoma brucei rhodesiense (ic50 = 3.7 microg/ml). bioassay-guided fractionation of the extract resulted in isolation of cinnamoylphenethyl amides, including n-trans-caffeoyltyramine (1), n-trans-p-coumaroyltyramine (7), and n-trans-feruloyltyramine (8) as the main active constituents (ic50s ranging from 2.2 to 13.3 microm). some structurally related, but less active compounds, such as ...201222816300
trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the hphb receptor implicated in human serum resistance.trypanosoma brucei rhodesiense (tbr) and t. b. gambiense (tbg), causative agents of human african trypanosomiasis (sleeping sickness) in africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (tlfs), components of innate immunity in human serum that protect against infection by other african trypanosomes. in tbr, lytic activity is suppressed by the tbr-specific serum-resistance associated (sra) protein. the mechanism in tbg is less well understood but ...201222802982
discovery of nitroheterocycles active against african trypanosomes. in vitro screening and preliminary sar studies.a selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite trypanosoma brucei rhodesiense, causative agent of human african trypanosomiasis (hat). the unspecific cytotoxicity of the compounds was also evaluated against rat myoblast l6-cells to measure the selectivity of the compounds towards the parasite. this screening revealed some preliminary structure-activity relationships (sar) among the series, and six hit compou ...201222738640
priorities for the elimination of sleeping sickness.sleeping sickness describes two diseases, both fatal if left untreated: (i) gambian sleeping sickness caused by trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) rhodesian sleeping sickness caused by t. b. rhodesiense, an acute disease with death occurring within weeks of infection. control of gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. in ...201222726645
an alternative form of melarsoprol in sleeping sickness.human african trypanosomiasis (hat), or sleeping sickness, is a major threat to human health throughout sub-saharan africa. almost always fatal if untreated or inadequately treated, a commonly used drug for treating late-stage hat, and the only drug for late-stage trypanosoma brucei rhodesiense, is intravenous melarsoprol, which kills 5% of patients receiving it. melarsoprol cyclodextrin inclusion complexes have been tested in a highly reliable mouse model of hat. these complexes increase the or ...201222704910
apol1 expression is induced by trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness.most african trypanosome species are sensitive to trypanolytic factors (tlfs) present in human serum. trypanosome lysis was demonstrated to be associated with apolipoprotein l-i (apol1). trypanosoma brucei (t. b.) gambiense and trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to apol1 mediated lysis. whereas t. b. rhodesiense resistance is linked with the expression of the serum resistance associated (sra) protein tha ...201222691369
modeling the control of trypanosomiasis using trypanocides or insecticide-treated livestock.in uganda, rhodesian sleeping sickness, caused by trypanosoma brucei rhodesiense, and animal trypanosomiasis caused by t. vivax and t. congolense, are being controlled by treating cattle with trypanocides and/or insecticides. we used a mathematical model to identify treatment coverages required to break transmission when host populations consisted of various proportions of wild and domestic mammals, and reptiles.201222616017
human african trypanosomiasis in a belgian traveller returning from the masai mara area, kenya, february 2012.a belgian traveller was diagnosed with human african trypanosomiasis (hat) due to trypanosoma brucei rhodesiense nine days after visiting the masai mara area in kenya. he presented with an inoculation chancre and was treated with suramin within four days of fever onset. two weeks earlier, hat was also reported in a german traveller who had visited the masai mara area. because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of hat.201222433595
trypanosoma brucei rhodesiense infection in a german traveller returning from the masai mara area, kenya, january 2012.in january 2012, a case of human african trypanosomiasis (hat) has been identified in germany in a traveller returning from the masai mara area in kenya. the 62-year-old man had travelled to the masai mara game park from 18 to 19 january 2012 and developed fever on 28 january. the infection with trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter.201222433594
synthesis and structure-activity relationships of new quinolone-type molecules against trypanosoma brucei.human african trypanosomiasis (hat) or sleeping sickness is caused by two subspecies of trypanosoma brucei , trypanosoma brucei gambiense , and trypanosoma brucei rhodesiense and is one of africa's old plagues. it causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library w ...201222376072
multiorgan dysfunction caused by travel-associated african trypanosomiasis.we describe a case of multiorgan dysfunction secondary to trypanosoma brucei rhodesiense infection acquired on safari in zambia. this case was one of several recently reported to promed-mail in persons who had traveled to this region. trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of africa.201222305185
cattle movements and trypanosomes: restocking efforts and the spread of trypanosoma brucei rhodesiense sleeping sickness in post-conflict uganda.the northwards spread of acute t. b. rhodesiense sleeping sickness in uganda has been linked to cattle movements associated with restocking following the end to military conflict in 2006. this study examined the number of cattle traded from t. b. rhodesiense endemic districts, the prevalence of the parasite in cattle being traded and the level of trypanocidal treatment at livestock markets.201324289452
population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci.african trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. trypanosoma brucei rhodesiense, which infects humans and livestock in east and southern africa, has classically been described as a host-range variant of the non-human infective trypanosoma brucei that occurs as stable clonal lineages. we have examined t. b. rhodesiense populations from east ...201324244771
il-6 is upregulated in late-stage disease in monkeys experimentally infected with trypanosoma brucei rhodesiense.the management of human african trypanosomiasis (hat) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. the search for novel biomarkers is, therefore, essential in the fight against hat. the current study aimed at investigating the potential of il-6 as an adjunct parameter for hat stage determination in vervet monkey model. four adult vervet monkeys (chlorocebus aethiops) were experimentally infected with trypanosoma brucei rhodesiense and treated subcuratively at ...201324194772
discovery and evaluation of thiazinoquinones as anti-protozoal agents.pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone a (2) to be a moderate growth inhibitor of trypanosoma brucei rhodesiense (ic₅₀ 3.1 μm) and plasmodium falciparum (k1 dual drug resistant strain) (ic₅₀ 3.3 μm) while exhibiting low levels of cytotoxicity (l6, ic₅₀ 167 μm). a series of c-7 amide and δ²(³) analogues were prepared that explored the influence of lipophilicity and oxidation state on observed anti-protozoal activity and selec ...201324022732
synthesis and antiprotozoal activity of dicationic 2,6-diphenylpyrazines and aza-analogues.dicationic 2,6-diphenylpyrazines, aza-analogues and prodrugs were synthesized; evaluated for dna affinity, activity against trypanosoma brucei rhodesiense (t. b. r.) and plasmodium falciparum (p. f.) in vitro, efficacy in t. b. r. stib900 acute and t. b. brucei gvr35 cns mouse models. most diamidines gave poly(da-dt)2 δtm values greater than pentamidine, ic50 values: t. b. r. (4.8-37nm) and p. f. (10-52nm). most diamidines and prodrugs gave cures for stib900 model (11, 19a and 24b 4/4 cures); 12 ...201324012380
antiprotozoal activity of bicyclic diamines with a n-methylpiperazinyl group at the bridgehead atom.ω-aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1-yl)bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2-azabicyclo[3.2.2]nonanes were prepared and their activities were examined in vitro against the multiresistant k1 strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900). some of the newly synthesized compounds showed very promising antiprotozoal activity and selectivity. a few of the alkylamino-2-azabicyclo[3.2.2]nonanes exhibited high ant ...201323880082
aminoalkyl derivatives of guanidine diaromatic minor groove binders with antiprotozoal activity.considering the strong dna minor groove binding observed for our previous series of diaromatic symmetric and asymmetric guanidinium and 2-aminoimidazolinium derivatives, we report now the synthesis of new aminoalkyl derivatives of diaromatic guanidines with potential as dna minor groove binders and antiprotozoal activity. the preparation of these aminoalkyl derivatives (12a-e, 13a-e, 14a-c,e, 15a-e, 16a-e) is presented as well as their affinity for dna which was evaluated by means of dna thermal ...201323301592
abietane diterpenoids from salvia sahendica--antiprotozoal activity and determination of their absolute configurations.in a screening of iranian plants for antiprotozoal activity, an n-hexane extract of the roots of salvia sahendica potently inhibited the growth of plasmodium falciparum k1 strain. subsequent hplc-based activity profiling led to the identification of seven known and one new abietane-type diterpenoid. structure elucidation was achieved by analysis of spectroscopic data including 1d and 2d nmr. the absolute configuration of sahandol (7) and sahandone (8) were assigned by comparison of experimental ...201323299758
domestic pigs as potential reservoirs of human and animal trypanosomiasis in northern tanzania.pig keeping is becoming increasingly common across sub-saharan africa. domestic pigs from the arusha region of northern tanzania were screened for trypanosomes using pcr-based methods to examine the role of pigs as a reservoir of human and animal trypanosomiasis.201324499540
the dispersal ecology of rhodesian sleeping sickness following its introduction to a new area.tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-saharan africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. the spread of rhodesian sleeping sickness (caused by trypanosoma brucei rhodesiense) within uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant re ...201324130913
sleeping sickness in buikwe south health sub-district: neuroinfection situation report.the aim of this paper is to describe the incidence of trypanosoma brucei rhodesiense sleeping sickness in the last functioning treatment centre in buikwe south hsd in southeast uganda, in mukono district, for a 19-year period (1989-2008). this is a report on the treatment outcome, structure of population affected, comparison with the published data on general incidence of t. b rhodesiensae in uganda and functioning of sleeping sickness control program.201324013601
antitrypanosomal triterpenoid with an ε-lactone e-ring from salvia urmiensis.a new triterpenoid, urmiensolide (1), was isolated from salvia urmiensis. the structure was elucidated by a combination of 1d and 2d nmr, hresims, and x-ray crystallographic analyses. the absolute configuration was established by comparison of experimental and simulated ecd spectra. urmiensolide is the first pentacyclic triterpenoid bearing a ε-lactone e-ring. the compound showed in vitro antitrypanosoal activity with an ic₅₀ value of 5.6 μm against the trypanosoma brucei rhodesiense stib 900 st ...201324007549
whole-genome sequencing of trypanosoma brucei reveals introgression between subspecies that is associated with virulence.human african trypanosomiasis is caused by two subspecies of trypanosoma brucei. trypanosoma brucei rhodesiense is found in east africa and frequently causes acute disease, while trypanosoma brucei gambiense is found in west africa and is associated with chronic disease. samples taken from a single focus of a ugandan outbreak of t. b. rhodesiense in the 1980s were associated with either chronic or acute disease. we sequenced the whole genomes of two of these isolates, which showed that they are ...201323963174
identification of trypanosome proteins in plasma from african sleeping sickness patients infected with t. b. rhodesiense.control of human african sleeping sickness, caused by subspecies of the protozoan parasite trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. to identify trypanosome proteins that have potential as biomarkers for detection and monitoring of african sleeping sickness, we have used a 'deep-mining" proteomics approach to identify trypanosome proteins in human plasma. abundant human plasma ...201323951171
a current analysis of chemotherapy strategies for the treatment of human african trypanosomiasis.despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human african trypanosomiasis (hat) remains a challenging task. the four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-saharan africa. pentamidine and suramin are limited by their effectiveness against the only first stage of trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, respectively. ...201323916333
glossina fuscipes populations provide insights for human african trypanosomiasis transmission in uganda.uganda has both forms of human african trypanosomiasis (hat): the chronic gambiense disease in the northwest and the acute rhodesiense disease in the south. the recent spread of rhodesiense into central uganda has raised concerns given the different control strategies the two diseases require. we present knowledge on the population genetics of the major vector species glossina fuscipes fuscipes in uganda with a focus on population structure, measures of gene flow between populations, and the occ ...201323845311
human african trypanosomiasis.human african trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-saharan africa. the disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. the disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal ...201323829907
preliminary investigation of trypanosomosis in exotic dog breeds from zambia's luangwa and zambezi valleys using lamp.abstract. canine african trypanosomosis (cat) is rarely reported in the literature. in this preliminary study, we evaluated the performance of loop-mediated isothermal amplification (lamp) against microscopy to detect cat in six exotic dog breeds naturally infected with trypanosomes from zambia's south luangwa national park and chiawa game management area. to our knowledge, this is the first report of cat in zambia. the patients exhibited a variety of aspecific clinical signs. the lamp did not o ...201323716412
2-arylpaullones are selective antitrypanosomal agents.antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human thp-1 cells. in order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. the most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophen ...201323648975
socio-economic and cultural determinants of human african trypanosomiasis at the kenya - uganda transboundary.kenya and uganda have reported different human african trypanosomiasis incidences in the past more than three decades, with the latter recording more cases. this cross-sectional study assessed the demographic characteristics, tsetse and trypanosomiasis control practices, socio-economic and cultural risk factors influencing trypanosoma brucei rhodesiense (t.b.r.) infection in teso and busia districts, western kenya and tororo and busia districts, southeast uganda. a conceptual framework was postu ...201323638206
new biomarkers for stage determination in trypanosoma brucei rhodesiense sleeping sickness patients.accurate stage determination is crucial in the choice of treatment for patients suffering from sleeping sickness, also known as human african trypanosomiasis (hat). current staging methods, based on the counting of white blood cells (wbc) and the detection of parasites in the cerebrospinal fluid (csf) have limited accuracy. we hypothesized that immune mediators reliable for staging t. b. gambiense hat could also be used to stratify t. b. rhodesiense patients, the less common form of hat.a popula ...201323369533
naphthoquinone derivatives exert their antitrypanosomal activity via a multi-target mechanism.recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. the lead of this series (b6, 2-phenoxy-1,4-naphthoquinone) showed an ed(50) of 80 nm against trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. a multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunc ...201323350008
new antiprotozoal agents: their synthesis and biological evaluations.here we report identification of new lead compounds based on quinoline and indenoquinolines with variable side chains as antiprotozoal agents. quinolines 32, 36 and 37 (table 1) and indenoquinoline derivatives 14 and 23 (table 2) inhibit the in vitro growth of the trypanosoma cruzi, trypanosoma brucei, trypanosoma brucei rhodesiense subspecies and leishmania infantum with ic50=0.25 μm. these five compounds have superior activity to that of the front-line drugs such as benznidazole, nifurtimox an ...201323518280
novel 3-nitro-1h-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against trypanosoma cruzi, the causative parasite of chagas disease. in the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional sars. all nitrotriazole-based derivatives were active or moderately active against t. cru ...201324012457
antiprotozoal screening of 60 south african plants, and the identification of the antitrypanosomal germacranolides schkuhrin i and ii.two hundred and seven extracts were prepared from sixty plants from south africa and screened for in vitro activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 21 extracts which inhibited the growth of one or more parasites with more than 95 % at 10 µg/ml, the ic50 values against all four protozoal parasites and cytotoxic ic50 values against l6 myoblasts were determined. amongst the most notable results are the activities of ...201323929246
synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives.sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs) were prepared and assayed for activities in vitro and in vivo against trypanosoma brucei rhodesiense (stib900), and in vitro against plasmodium falciparum (k1) and leishmania donovani axenic amastigotes. 3-amidinobenzyl 4-amidino-2-iodo-6-methoxyphenyl ether dihydrochloride (55, ic50 = 3.0 nm) and seven other compounds exhibited ic50 values below 10 nm against t. b. rhodesiense in vitro. the 2-bromo-4,4'-diamidino a ...201323871911
3-(oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid trypanosoma brucei, the causative agent for human african trypanosomiasis.a whole organism high-throughput screen of approximately 87,000 compounds against trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. herein we report a structure-activity relationship (sar) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]pyridin-2-yl)anilides. sharp sar is revealed, with our most active compound (5) exhibiting an ic₅ ...201323831695
antiprotozoal isoflavan quinones from abrus precatorius ssp. africanus.a library of 206 extracts from selected south african plants was screened in vitro against a panel of protozoan parasites, plasmodium falciparum, trypanosoma brucei rhodesiense, and leishmania donovani. a ch2cl2/meoh (1 : 1) extract of abrus precatorius l. ssp. africanus strongly inhibited p. falciparum (98 %), t. b. rhodesiense (100 %), and l. donovani (76 %) when tested at a concentration of 10.0 µg/ml. the active constituents were tracked by hplc-based activity profiling and isolated by prepa ...201323512498
antiprotozoal activity of khaya anthotheca, (welv.) c.d.c. a plant used by chimpanzees for self-medication.khaya species, endemic to africa and madagascar, continues to be valuable in indigenous traditional medicine. their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. in the budongo rain forest of western uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed.201323501156
anti-protozoal activity of aporphine and protoberberine alkaloids from annickia kummeriae (engl. & diels) setten & maas (annonaceae).malaria, trypanosomiasis and leishmaniasis have an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. currently, there is inadequate armory of drugs for the treatment of malaria, trypanosomiasis and leishmaniasis. this underscores the continuing need for the discovery and development of new anti-protozoal drugs. consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe ...201323445637
eleganolone, a diterpene from the french marine alga bifurcaria bifurcata inhibits growth of the human pathogens trypanosoma brucei and plasmodium falciparum.organic extracts of 20 species of french seaweed have been screened against trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. these extracts have previously shown potent antiprotozoal activities in vitro against plasmodium falciparum and leishmania donovani. the selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian l6 cell line. the ethyl acetate extract of the brown seaweed, bifurcaria bifurcata, showed strong trypano ...201323442789
investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents.pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine a and b (2 and 3) to be weak growth inhibitors of trypanosoma brucei rhodesiense (ic50 59 and 44 μm, respectively) and plasmodium falciparum (k1 dual drug resistant strain) (ic50 41 and 15 μm, respectively), but lacking in selectivity (l6 rat myoblast, ic50 24 μm and 25 μm, respectively). to expand the structure-activity relationship of this compound class towards both parasites, w ...201424879541
procerenone: a fatty acid triterpenoid from the fruit pericarp of omphalocarpum procerum (sapotaceae).phytochemical investigation of a dichloromethane-methanol (1:1) extract of the fruit pericarp of omphalocarpum procerum which exhibited antiplasmodial activity during preliminary screening led to the isolation of the new fatty ester triterpenoid 3β-hexadecanoyloxy-28-hydroxyolean-12-en-11-one (1), together with five known compounds 2-6. the structure of the new compound as well as those of the known compounds was established by means of spectroscopic methods and by comparison with previously rep ...201425587333
novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against trypanosoma cruzi, the causative parasite of chagas disease. more importantly, several such analogs displayed significant antichagasic activity in vivo, superior to that of benznidazole, the current clinical standard. we now report the synthesis and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamid ...201425240098
hplc-based activity profiling for antiplasmodial compounds in the traditional indonesian medicinal plant carica papaya l.leaf decoctions of carica papaya have been traditionally used in some parts of indonesia to treat and prevent malaria. leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo.201424892830
synthesis and antiparasitic activity of new bis-arylimidamides: db766 analogs modified in the terminal groups.fifteen novel bis-arylimidamide derivatives with various 6-membered (7a-c) and 5-membered (7d-o) heterocyclic rings replacing the terminal pyridyl rings of the lead compound db766{(2,5-bis[2-i-propoxy-4-(2-pyridylimino)aminophenylfuran]}, were prepared and evaluated versus trypanosoma cruzi, leishmania amazonensis, trypanosoma brucei rhodesiense and plasmodium falciparum. compound 7a with pyrimidine replacing the pyridine rings showed good activity versus t. cruzi, t. brucei rhodesiense and p. f ...201424956553
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 ...201424411022
activity of diimidazoline amides against african trypanosomiasis.we identified several diimidazoline mono- and diamides that were as potent as pentamidine against trypanosoma brucei rhodesiense in vitro. all of these were also less cytotoxic than pentamidine, but none was as effective as the latter in a t. brucei rhodesiense-infected mouse model. a single imidazoline may be sufficient for high antitrypanosomal activity provided that a second weak base functional group is present.201424398295
antitrypanosomal isoflavan quinones from abrus precatorius.human african trypanosomiasis is a neglected tropical disease in sub saharan africa that is fatal if left untreated. in a search for new natural products with antitrypanosomal activity, we recently identified abruquinones b and i from abrus precatorius as potent in vitro trypanocidal compounds with high selectivity indices. to obtain sufficient compound for in vivo efficacy tests in mice, a second batch of plant material was re-collected and extracted. however, the chemical profiles of the two b ...201424382449
increased burden of cardiovascular disease in carriers of apol1 genetic variants.two distinct alleles in the gene encoding apolipoprotein l1 (apol1), a major component of high-density lipoprotein, confer protection against trypanosoma brucei rhodesiense infection and also increase risk for chronic kidney disease. approximately 14% of americans with african ancestry carry 2 apol1 risk alleles, accounting for the high chronic kidney disease burden in this population.201424379297
antitrypanosomal isothiocyanate and thiocarbamate glycosides from moringa peregrina.o-methyl (1), o-ethyl (2), and o-butyl (3) 4-[(α-l-rhamnosyloxy) benzyl] thiocarbamate (e), along with 4-(α-l-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of moringa peregrina. the compounds were tested for in vitro activity against trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (l6 cells). the most potent compound was 4 with an ic50 of 0.10 µm against t.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides ...201424310210
the burden and spatial distribution of bovine african trypanosomes in small holder crop-livestock production systems in tororo district, south-eastern uganda.african animal trypanosomiasis (aat) is considered to be one of the greatest constraints to livestock production and livestock-crop integration in most african countries. south-eastern uganda has suffered for more than two decades from outbreaks of zoonotic human african trypanosomiasis (hat), adding to the burden faced by communities from aat. there is insufficient aat and hat data available (in the animal reservoir) to guide and prioritize aat control programs that has been generated using con ...201425532828
midgut expression of immune-related genes in glossina palpalis gambiensis challenged with trypanosoma brucei gambiense.tsetse flies from the subspecies glossina morsitans morsitans and glossina palpalis gambiensis, respectively, transmit trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. the former causes the acute form of sleeping sickness, and the latter provokes the chronic form. although several articles have reported g. m. morsitans gene expression following trypanosome infection, no comparable investigation has been performed for g. p. gambiensis. this report presents results on the different ...201425426112
epidemiology of human african trypanosomiasis.human african trypanosomiasis (hat), or sleeping sickness, is caused by trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central africa, and by trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern africa. the rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the diseas ...201425125985
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 ...201424978605
the molecular arms race between african trypanosomes and humans.humans can survive bloodstream infection by african trypanosomes, owing to the activity of serum complexes that have efficient trypanosome-killing ability. the two trypanosome subspecies that are responsible for human sleeping sickness--trypanosoma brucei rhodesiense and trypanosoma brucei gambiense--can evade this defence mechanism by expressing distinct resistance proteins. in turn, sequence variation in the gene that encodes the trypanosome-killing component in human serum has enabled populat ...201424975321
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 ...201424830321
evolution of the primate trypanolytic factor apol1.apolipoproteinl1 (apol1) protects humans and some primates against several african trypanosomes. apol1 genetic variants strongly associated with kidney disease in african americans have additional trypanolytic activity against trypanosoma brucei rhodesiense, the cause of acute african sleeping sickness. we combined genetic, physiological, and biochemical studies to explore coevolution between the apol1 gene and trypanosomes. we analyzed the apol1 sequence in modern and archaic humans and baboons ...201424808134
plasma neuronal specific enolase: a potential stage diagnostic marker in human african trypanosomiasis.this study was carried out to determine the potential of neuronal specific enolase (nse) as a stage diagnostic marker in human african trypanosomiasis.201424789741
two trypanocidal dipeptides from the roots of zapoteca portoricensis (fabaceae).zapoteca portoricensis (jacq) hm hernández is used with remarkable efficacy in ethnomedicinal management of tonsillitis in the eastern part of nigeria. previous pharmacological studies have validated the antiinflammatory and antimicrobial activities of the crude extract. in this study, two dipeptides, saropeptate (aurantiamide acetate) and anabellamide, were isolated from the methanol root extract of zapoteca portoricensis and their chemical structures deduced by one dimensional and two dimensio ...201424776813
modelling the use of insecticide-treated cattle to control tsetse and trypanosoma brucei rhodesiense in a multi-host population.we present a mathematical model for the transmission of trypanosoma brucei rhodesiense by tsetse vectors to a multi-host population. to control tsetse and t. b. rhodesiense, a proportion, ψ, of cattle (one of the hosts considered in the model) is taken to be kept on treatment with insecticides. analytical expressions are obtained for the basic reproduction number, r0n in the absence, and r(0n)(t) in the presence of insecticide-treated cattle (itc). stability analysis of the disease-free equilibr ...201424584715
clinical presentation of human african trypanosomiasis in zambia is linked to the existence of strains of trypanosoma brucei rhodesiense with varied virulence: two case reports.trypanosoma brucei rhodesiense typically causes acute and severe human african trypanosomiasis in zambia and other countries in eastern and southern africa. although a few atypical cases of chronic and mild forms of this disease were reported in zambia more than 40 years ago, no such cases have been diagnosed over the last four decades.201424529084
sodalis glossinidius prevalence and trypanosome presence in tsetse from luambe national park, zambia.tsetse flies are the biological vectors of african trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals. the tsetse endosymbiont sodalis glossinidius has been suggested to play a role in tsetse susceptibility to infection. here we investigate the prevalence of african trypanosomes within tsetse from the luambe national park, zambia and if there is an association between s. glossinidius and presence of trypanosomes within the tsetse examined.201425138709
1,2-substituted 4-(1h)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro.a diverse array of 4-(1h)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against plasmodium falciparum and trypanosoma brucei rhodesiense, and cytotoxicity against l-6 cells in vitro. furthermore, selectivity indices were also determined for both parasites. all compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against l-6 cells. compound 5a was found to be ...201425211002
antiprotozoal activity of achillea ptarmica (asteraceae) and its main alkamide constituents.in the course of our ongoing screening of plants of the family asteraceae for antiprotozoal activity, a ch2cl2-extract from the flowering aerial parts of achillea ptarmica l. (sneezewort yarrow) was found to be active in vitro against trypanosoma brucei rhodesiense (ic50 = 0.67 µg/ml) and plasmodium falciparum (ic50 = 6.6 μg/ml). bioassay guided fractionation led to the isolation and identification of five alkamides from the most active fractions. pellitorine and 8,9-z-dehyropellitorine are the ...201424853616
antiprotozoal activity of dicationic 3,5-diphenylisoxazoles, their prodrugs and aza-analogues.fifty novel prodrugs and aza-analogues of 3,5-bis(4-amidinophenyl)isoxazole and its derivatives were prepared. eighteen of the 24 aza-analogues exhibited ic₅₀ values below 25 nm against trypanosoma brucei rhodesiense or plasmodium falciparum. six compounds had antitrypanosomal ic₅₀ values below 10 nm. twelve analogues showed similar antiplasmodial activities, including three with sub-nanomolar potencies. forty-four diamidines (including 16 aza-analogues) and the 26 prodrugs were evaluated for ef ...201424268543
in silico prediction and experimental evaluation of furanoheliangolide sesquiterpene lactones as potent agents against trypanosoma brucei rhodesiense.as a continuation of our earlier study on the in vitro antiprotozoal activity of 40 natural sesquiterpene lactones (stls), we extended the set of tested compounds from our laboratories to 59. on the basis of this extended data set, further enriched by literature data for 10 compounds tested under the same conditions, our quantitative structure-activity relationship (qsar) analyses for activity against t. brucei rhodesiense (etiologic agent of human african trypanosomiasis, or sleeping sickness) ...201424165182
discovery of infection associated metabolic markers in human african trypanosomiasis.human african trypanosomiasis (hat) remains a major neglected tropical disease in sub-saharan africa. as clinical symptoms are usually non-specific, new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment. this is particularly important for disease caused by trypanosoma brucei rhodesiense, where indirect immunodiagnostic approaches have to date been unsuccessful. we have conducted global metabolic profiling of plasma from t.b.rho ...201526505639
discovery of inhibitors of trypanosoma brucei by phenotypic screening of a focused protein kinase library.a screen of a focused kinase inhibitor library against trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. screening of these hits in a t. b. brucei proliferation assay highlighted three compounds with a 1h-imidazo[4,5-b]pyrazin-2(3h)-one scaffold that showed sub-micromolar activity and excellent selectivity against the mrc5 cell line. subsequent rounds of optimisation led to the identification of compounds that ...201526381210
identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain.rhodesain, the major cathepsin l-like cysteine protease in the protozoan trypanosoma brucei rhodesiense, the causative agent of african sleeping sickness, is a well-validated drug target. in this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of t. brucei. to discover inhibitors active against rhodesain and t. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary sar studies. we envisio ...201526342866
comparative analysis of cerebrospinal fluid from the meningo-encephalitic stage of t. b. gambiense and rhodesiense sleeping sickness patients using tmt quantitative proteomics.the quantitative proteomics data here reported are part of a research article entitled "increased acute immune response during the meningo-encephalitic stage of trypanosoma brucei rhodesiense sleeping sickness compared to trypanosoma brucei gambiense", published by tiberti et al., 2015. transl. proteomics 6, 1-9. sleeping sickness (human african trypanosomiasis - hat) is a deadly neglected tropical disease affecting mainly rural communities in sub-saharan africa. this parasitic disease is caused ...201526306311
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. ...201526247439
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 ...201526110113
comparative pathogenicity of trypanosoma brucei rhodesiense strains in swiss white mice and mastomys natalensis rats.we evaluated mastomys natelensis rat as an animal model for rhodesian sleeping sickness. parasitaemia, clinical and pathological characteristics induced by t. b. rhodesiense isolates, ketri 3439, 3622 and 3637 were compared in mastomys rats and swiss white mice. each isolate was intra-peritonially injected in mice and rat groups (n=12) at 1×10(4) trypanosomes/0.2ml. pre-patent period (pp) range for ketri 3439 and ketri 3622-groups was 3-6 days for mice and 4-5 days for rats while for ketri 3637- ...201526099681
interleukin (il)-6 and il-10 are up regulated in late stage trypanosoma brucei rhodesiense sleeping sickness.sleeping sickness due to trypanosoma brucei rhodesiense has a wide spectrum of clinical presentations coupled with differences in disease progression and severity across east and southern africa. the disease progresses from an early (hemo-lymphatic) stage to the late (meningoencephalitic) stage characterized by presence of parasites in the central nervous system. we hypothesized that disease progression and severity of the neurological response is modulated by cytokines.201526090964
determination of the prevalence of trypanosome species in cattle from monduli district, northern tanzania, by loop mediated isothermal amplification.bovine african trypanosomosis (bat) remains one of the major vector-borne diseases with serious impediment to cattle production and economic advancement in sub-saharan africa. the present study evaluated the performance of the trypanosome-species-specific loop-mediated isothermal amplification (lamp), using parasite dna obtained from 295 indigenous tanzanian short horn zebu (tshz) and boran crosses in monduli district within northern tanzania, against routine microscopy on giemsa-stained blood f ...201525953023
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 ...201525924022
how can molecular diagnostics contribute to the elimination of human african trypanosomiasis?a variety of molecular diagnostic tests for human african trypanosomiasis (hat) (sleeping sickness) has been developed. some are effectively used for research and confirmation diagnosis in travel medicine, usually following non-standardized protocols. others have become commercially available as diagnostic kits. who aims to eliminate hat as a public health problem by the year 2020, and zero transmission by the year 2030. this article gives an overview of the recent progress in molecular diagnost ...201525786994
anti-trypanosomal cadinanes synthesized by transannular cyclization of the natural sesquiterpene lactone nobilin.acid-catalyzed transannular cyclization of the germacrene-type sesquiterpene lactone nobilin 1 was investigated with the aim of obtaining new anti-trypanosomal cadinane derivatives. the reaction was regiospecific in all tested reaction conditions. compounds were fully characterized by spectroscopic and computational methods, and the anti-trypanosomal activity was evaluated and compared to nobilin (ic50 3.19±1.69μm). the tricyclic derivative 11 showed most potent in vitro activity against trypano ...201525740635
clinical profiles, disease outcome and co-morbidities among t. b. rhodesiense sleeping sickness patients in uganda.the acute form of human african trypanosomiasis (hat, also known as sleeping sickness) caused by trypanosoma brucei rhodesiense has been shown to have a wide spectrum of focus specific clinical presentation and severity in east and southern africa. indeed hat occurs in regions endemic for other tropical diseases, however data on how these co-morbidities might complicate the clinical picture and affect disease outcome remains largely scanty. we here describe the clinical presentation, presence of ...201525719539
a co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome.trypanosoma brucei is the causative agent of african sleeping sickness in humans and one of several pathogens that cause the related veterinary disease nagana. a complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. the first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-l1 (apol1) found within two serum protein complexes, trypanosome lyti ...201525656360
metabolic syndrome: an ill wind that blows some good?in this issue of the journal, brima et al. report thought-provoking research providing a potential evolutionary rationale whereby natural selection might have preserved genes that predispose to metabolic syndrome. when cd-1 mice were fed a high fat diet, this induced metabolic changes characteristic of metabolic syndrome. in addition, the high fat diet provided substantial protection from lethality due to infection with trypanosoma cruzi. the authors hypothesize that the same genes predispose to ...201525611014
african trypanosome-induced blood-brain barrier dysfunction under shear stress may not require erk activation.african trypanosomes are tsetse fly transmitted protozoan parasites responsible for human african trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. how the parasites under microvascular shear stress (ss) flow conditions in the brain cross the blood-brain barrier (bbb) is not known. in vitro studies using static models comprised of human brain microvascular endothelial cells (bmec) show that bbb activation and crossing by trypanosomes requires the orchestr ...201527053915
transcriptomes of newly-isolated trypanosoma brucei rhodesiense reveal hundreds of mrnas that are co-regulated with stumpy-form markers.during natural trypanosoma brucei infections, the parasites differentiate spontaneously into a non-dividing "stumpy" form when a certain level of parasitaemia is attained. this form is metabolically adapted for rapid further differentiation into procyclic forms upon uptake by tsetse flies.201526715446
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 ...201525421467
escape mechanisms of african trypanosomes: why trypanosomosis is keeping us awake.african trypanosomes have been around for more than 100 million years, and have adapted to survival in a very wide host range. while various indigenous african mammalian host species display a tolerant phenotype towards this parasitic infection, and hence serve as perpetual reservoirs, many commercially important livestock species are highly disease susceptible. when considering humans, they too display a highly sensitive disease progression phenotype for infections with trypanosoma brucei rhode ...201525479093
3-nitrotriazole-based piperazides as potent antitrypanosomal agents.novel linear 3-nitro-1h-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. in addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. most 3-nitrotriazole-based derivatives were potent and selective against trypanosoma cruzi parasites, but only one displayed these desired properties against trypanosoma brucei rhodesiense. moreover, two 3-nitrotriazole-based chlorophenylpiperazides were mod ...201526363868
discovery of potent nitrotriazole-based antitrypanosomal agents: in vitro and in vivo evaluation.3-nitro-1h-1,2,4-triazole- and 2-nitro-1h-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. all 3-nitrotriazole-based derivatives were extremely potent anti-trypanosoma cruzi agents at sub nm concentrations and exhibited a high degree of selectivity for the parasite. the 2-nitroimidazole analogs were only moderately active against t. cruzi amastigotes and exhibited low selectivity. both types of compound were active against leishmania d ...201526344593
search for antiprotozoal activity in herbal medicinal preparations; new natural leads against neglected tropical diseases.sleeping sickness, chagas disease, leishmaniasis, and malaria are infectious diseases caused by unicellular eukaryotic parasites ("protozoans"). the three first mentioned are classified as neglected tropical diseases (ntds) by the world health organization and together threaten more than one billion lives worldwide. due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. in vie ...201526248069
2-phenoxy-1,4-naphthoquinones: from a multitarget antitrypanosomal to a potential antitumor profile.a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound b6 (1). the whole series was evaluated against the three most important human trypanosomatid pathogens (trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. furthermore, a subset also inh ...201526237241
anti-protozoal activities of cembrane-type diterpenes from vietnamese soft corals.based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as trypanosoma and plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the vietnamese sea to an in vitro screening for anti-protozoal activity against trypanosoma brucei rhodesiense (tbr), t. cruzi (tc), leishmania donovani (ld), and plasmodium falciparum (pf). twelve of the tested compounds displayed significant ...201526184133
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