| 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 ... | 2015 | 26237241 |
| 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 ... | 2015 | 26184133 |
| macyranones: structure, biosynthesis, and binding mode of an unprecedented epoxyketone that targets the 20s proteasome. | in our screening efforts to identify unique scaffolds from myxobacteria for the drug discovery process, we used lc-spe-nmr-ms techniques to isolate six linear peptides, termed macyranone a-f, from cystobacter fuscus mcy9118. the macyranones are characterized by a rare 2-methylmalonamide moiety and an α-amino ketone fragment including an α',β'-epoxyketone in macyranone a. gene disruption experiments confirmed the biosynthetic gene cluster of the macyranones as pks/nrps hybrid. detailed in silico ... | 2015 | 26050527 |
| pls-prediction and confirmation of hydrojuglone glucoside as the antitrypanosomal constituent of juglans spp. | naphthoquinones (nqs) occur naturally in a large variety of plants. several nqs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human african trypanosomiasis (sleeping sickness), chagas disease and leishmaniasis. prominent nq-producing plants can be found among juglans spp. (juglandaceae) with juglone derivatives as known constituents. in this study, 36 highly variable extracts were prepared from different plant parts of j. regia, ... | 2015 | 26035104 |
| predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through qsar multi-target and molecular topology. | multi-target qsar is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. in this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target qsar model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. the activity was related to three parasites with a high prevalence rate ... | 2015 | 25754076 |
| antiprotozoal activity and dna binding of dicationic acridones. | dicationic acridone derivatives were synthesized and their antiparasitic activity was evaluated. acridones displayed in vitro nanomolar ic50 values against trypanosoma brucei rhodesiense stib900 with selectivity indices >1000. compounds 1b, 3a, and 3b were as potent as the reference drug melarsoprol in this assay. submicromolar-range activities were observed against wild-type (nf54) and resistant (k1) strains of plasmodium falciparum, whereas no significant activity was detected against trypanos ... | 2015 | 25642604 |
| 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 ... | 2014 | 25587333 |
| 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 ... | 2014 | 25240098 |
| 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. | 2014 | 24892830 |
| 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 ... | 2013 | 24012457 |
| 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 ... | 2013 | 23929246 |
| 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 ... | 2013 | 23871911 |
| 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 ... | 2013 | 23831695 |
| 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 ... | 2013 | 23512498 |
| 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. | 2013 | 23501156 |
| 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 ... | 2013 | 23445637 |
| 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 ... | 2013 | 23442789 |
| conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile. | a combinatorial library of quinone-polyamine conjugates designed to optimize the antitrypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid-phase approach. the conjugates were evaluated against the three most important human trypanosomatid pathogens (trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishmania donovani), and several showed promising activity. a subset also inhibited trypanothione reductase in vitro and induced oxidase activity of the enzyme. a highly p ... | 2012 | 23153330 |
| marchantin a, a macrocyclic bisbibenzyl ether, isolated from the liverwort marchantia polymorpha, inhibits protozoal growth in vitro. | in vitro anti-plasmodial activity-guided fractionation of a diethyl ether extract of the liverwort species marchantia polymorpha, collected in iceland, led to isolation of the bisbibenzyl ether, marchantin a. the structure of marchantin a (1) was confirmed by nmr and hreims. marchantin a inhibited proliferation of the plasmodium falciparum strains, nf54 (ic(50)=3.41μm) and k1 (ic(50)=2.02μm) and showed activity against other protozoan species trypanosoma brucei rhodesiense, t. cruzi and leishman ... | 2012 | 22951393 |
| 2-alkynoic fatty acids inhibit topoisomerase ib from leishmania donovani. | 2-alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. in this work we synthesized the 2-octadecynoic acid (2-oda), 2-hexadecynoic acid (2-hda), and 2-tetradecynoic acid (2-tda) and show that 2-oda is the best inhibitor of the leishmania donovani dna topoisomerase ib enzyme (ldtopib) with an ec(50)=5.3±0.7μm. the potency of ldtopib inhibition follows the trend 2-oda>2-hda>2-tda, indicating that the e ... | 2012 | 22932312 |
| manadoperoxides, a new class of potent antitrypanosomal agents of marine origin. | chemical investigation of the marine sponge plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides b-k (3-5 and 7-13) and peroxyplakoric esters b(3) (6) and c (14). eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing thf-type ring in the side chain. the library of endoperoxide derivatives was evaluated for in vitro activity against trypanosoma brucei rhodesiense and leishmania donovani. some compounds, such as manadopero ... | 2012 | 22859016 |
| novel 3-nitro-1h-1,2,4-triazole-based amides and sulfonamides as potential antitrypanosomal agents. | a series of novel 3-nitro-1h-1,2,4-triazole-based (and in some cases 2-nitro-1h-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. out of 36 compounds tested, 29 (mostly 3-nitro-1h-1,2,4-triazoles) displayed significant activity against trypanosoma cruzi intracellular amastigotes (ic(50) ranging from 28 nm to 3.72 μm) without concomitant toxicity to l6 host cells (selectivity 66-2782). twen ... | 2012 | 22550999 |
| synthesis, biological evaluation, and structure-activity relationships of n-benzoyl-2-hydroxybenzamides as agents active against p. falciparum (k1 strain), trypanosomes, and leishmania. | in our efforts to identify novel chemical scaffolds for the development of new antiprotozoal drugs, a compound library was screened against toxoplasma gondii tachyzoites with activity discovered for n-(4-ethylbenzoyl)-2-hydroxybenzamide 1a against t. gondii as described elsewhere. synthesis of a compound set was guided by t. gondii sar with 1r found to be superior for t. gondii , also active against thai and sierra leone strains of plasmodium falciparum , and with superior admet properties as de ... | 2012 | 22352841 |
| synthesis and antimalarial and antituberculosis activities of a series of natural and unnatural 4-methoxy-6-styryl-pyran-2-ones, dihydro analogues and photo-dimers. | previous studies have identified the 3,6-dialkyl-4-hydroxy-pyran-2-one marine microbial metabolites pseudopyronines a and b to be modest growth inhibitors of mycobacterium tuberculosis and a range of tropical diseases including plasmodium falciparum and leishmania donovani. in an effort to expand the structure-activity relationship of this compound class towards infectious diseases, a library of natural product and natural product-like 4-methoxy-6-styryl-pyran-2-ones and a subset of catalyticall ... | 2012 | 22285027 |
| 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 ... | 2013 | 23518280 |
| gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents. | gold compounds form a new class of promising metal-based drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. previous research revealed that a group of structurally diverse gold compounds cause conspicuous inhibition of the protease activities of the human proteasome. given the pharmacological importance of protease inhibition, the present study further explored whether these gold compounds might inhibit a few other pr ... | 2017 | 28283781 |
| structure elucidation and activity of kolossin a, the d-/l-pentadecapeptide product of a giant nonribosomal peptide synthetase. | the largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. it consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium photorhabdus luminescens. the identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. although it belongs to t ... | 2015 | 26118790 |
| synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities. | several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. the new compounds were tested for their activities against one strain of the causative organism of malaria tropica, plasmodium falciparum k1, which is resistant against chloroquine and pyrimethamine. in addition, their cytotoxicity and their activity against the pathogen of the east african form of sleeping sickness, trypanosoma brucei rhodesiense, were investigated. structure-activity relationships are discussed conside ... | 2015 | 25746816 |
| 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 ... | 2014 | 24879541 |
| agrochemicals against malaria, sleeping sickness, leishmaniasis and chagas disease. | in tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and chagas disease standing in the forefront. many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. in order to identify new antiprotozoal agents, more than 600 co ... | 2012 | 23145187 |
| new derivatives of 7-chloroquinolin-4-amine with antiprotozoal activity. | novel ω-aminoacyl and -alkyl derivatives of 7-chloroquinolin-4-amine were prepared and their structures confirmed by nmr spectroscopy. their antiprotozoal activities were examined in vitro against the sensitive nf54 strain as well as against the multiresistant k1 strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900). the results were compared with the activities of clinically used drugs. their antitrypanosomal activities were only moderate whereas their antiplasmo ... | 2017 | 28031151 |
| the production and antiprotozoal activity of abietane diterpenes in salvia austriaca hairy roots grown in shake flasks and bioreactor. | the biomass and concentration of bioactive quinone methide-type diterpenes in hairy roots of salvia austriaca were determined and compared with levels of these metabolites in roots of field-grown plants. the cultures were maintained in shake flasks and a nutrient sprinkle bioreactor. diterpene production was more efficient in the shake flask root culture than the bioreactor one. biomass and diterpene production within the shake flask culture was evaluated using schenk and hildebrandt (sh), gambo ... | 2017 | 27070932 |
| the antiprotozoal potencies of newly prepared 3-azabicyclo[3.2.2]nonanes. | 3-azabicyclo[3.2.2]nonanes are already reported as antiprotozoal agents. structural variations were performed by attachment of several basic side chains, being part of drugs in use, to the ring nitrogen. the structures of the new compounds were established using one and two dimensional nmr measurements. all compounds were investigated for their antiplasmodial and antitrypanosomal activities against plasmodium falciparum k 1 (multiresistant) and trypanosoma brucei rhodesiense. their cytotoxicity ... | 2016 | 27585596 |
| synthesis and potent antiprotozoal activity of mono/di amidino 2-anilinobenzimidazoles versus plasmodium falciparum and trypanosoma brucei rhodesiense. | a series of mono and dicationic new 2-anilinobenzimidazole carboxamidines were prepared in a four step process starting from 4-amino-3-nitrobenzonitrile and corresponding o-phenylenediamines. their antiparasitic activity against plasmodium falciparum (p. falciparum) and trypanosoma brucei rhodesiense (t.b. rhodesiense) were evaluated in vitro. some of the dicationic compounds (10,12,14) showed equal or very close activity against t.b. rhodesiense with melarsoprol and also showed promising activi ... | 2016 | 27387356 |
| antiprotozoal activity of bicycles featuring a dimethylamino group at their bridgehead. | several dimethylamino-derivatives of the new compound-class 3-azabicyclo[3.2.2]nonanes were prepared. for better comparison of activity also a few analogues of bicyclo[2.2.2]octanes and 2-azabicyclo[3.2.2]nonanes were synthesized. their activities were examined in vitro against the multiresistant k1 strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900). a couple of the newly synthesized compounds showed promising antiprotozoal activity and selectivity. the results ... | 2016 | 27344215 |
| a new alkamide with an endoperoxide structure from acmella ciliata (asteraceae) and its in vitro antiplasmodial activity. | from the aerial parts of acmella ciliata (h.b.k.) cassini (basionym spilanthes ciliata kunth; asteraceae), three alkamides were isolated and identified by mass- and nmr spectroscopic methods as (2e,6e,8e)-n-isobutyl-2,6,8-decatrienamide (spilanthol, (1)), n-(2-phenethyl)-2e-en-6,8-nonadiynamide (2) and (2e,7z)-6,9-endoperoxy-n-isobutyl-2,7-decadienamide (3). while 1 and 2 are known alkamides, compound 3 has not been described until now. it was found that the unusual cyclic peroxide 3 exists as a ... | 2016 | 27294907 |
| antiprotozoal selectivity of diimidazoline n-phenylbenzamides. | we discovered three diimidazolines with high antiplasmodial selectivity that had ic50 values of 1.9-28 nm against cultured plasmodium falciparum. we also identified a gem-dimethyl diimidazoline with high antitrypanosomal selectivity that had an ic50 value of 26 nm against cultured trypanosoma brucei rhodesiense. two 2-imidazoline heterocycles in a para orientation on a n-phenylbenzamide or similar core structure were required for high antiprotozoal activity. ring expansion of the imidazoline as ... | 2015 | 27622464 |
| role of moving average analysis for development of multi-target (q)sar models. | in modern drug discovery era, multi target- quantitative structure activity relationship [mt- (q)sar] approaches have emerged as novel and powerful alternatives in the field of in-silico drug design so as to facilitate the discovery of new chemical entities with multiple biological activities. amongst various machine learning approaches, moving average analysis (maa) has frequently exhibited high accuracy of prediction of diverse biological activities against different biological targets and exp ... | 2015 | 25694075 |
| exploring in vitro and in vivo hsp90 inhibitors activity against human protozoan parasites. | a set of compounds, previously selected as potent hsp90α inhibitors, has been studied on a panel of human parasites. 5-aryl-3,4-isoxazolediamide derivatives (1) were active against two protozoa, trypanosoma brucei rhodesiense and plasmodium falciparum, with a good tolerability toward cytotoxicity on non-malignant l6 rat myoblast cell line, unlike the 1,5-diaryl,4-carboxamides-1,2,3-triazole derivatives (2) which, while showing a single-digit nm range activity against the same protozoa, were also ... | 2015 | 25547934 |
| synthesis and antiprotozoal activities of new 3-azabicyclo[3.2.2]nonanes. | some antimalarial agents in use typically bear basic side chains as ligands. such ligands were attached to the amino substituent of a bridgehead atom of already antiprotozoal active 3-azabicyclo[3.2.2]nonanes. structure verification was done by nmr measurements. the new compounds were tested for their antiplasmodial and antitrypanosomal activities against plasmodium falciparum k 1 (multiresistant) and trypanosoma brucei rhodesiense as well as for their cytotoxicity against l6 cells. their activi ... | 2015 | 25433423 |
| 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 ... | 2014 | 25211002 |
| 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 ... | 2014 | 24853616 |
| 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 ... | 2014 | 24268543 |
| 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 ... | 2013 | 24022732 |
| 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 ... | 2013 | 24012380 |
| 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 ... | 2013 | 23880082 |
| 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 ... | 2013 | 23301592 |
| 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 ... | 2013 | 23299758 |
| isothermal microcalorimetry, a new tool to monitor drug action against trypanosoma brucei and plasmodium falciparum. | isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. the metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. in this study, we investigated the heat flow of two medically important protozoans, trypanosoma brucei rhodesiense and plasmodium falciparum. heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time ba ... | 2012 | 22679520 |
| cynaropicrin: the first plant natural product with in vivo activity against trypanosoma brucei. | a screen of 1800 plant and fungal extracts with subsequent hplc-based activity profiling was done to identify new antiprotozoal leads from nature. this led to the identification of cynaropicrin (1) from the herb centaurea salmantica l. (asteraceae) as a potent in vitro inhibitor of trypanosoma brucei rhodesiense. it preferentially inhibited t. b. rhodesiense (ic (50) of 0.3 µm) and t. brucei gambiense (ic (50) of 0.2 µm), compared to trypanosoma cruzi (ic (50) of 4.4 µm) and plasmodium falciparu ... | 2012 | 22331812 |
| 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. | 2014 | 25138709 |
| evaluating the impact of targeting livestock for the prevention of human and animal trypanosomiasis, at village level, in districts newly affected with t. b. rhodesiense in uganda. | uganda has suffered from a series of epidemics of human african trypanosomiasis (hat), a tsetse transmitted disease, also known as sleeping sickness. the area affected by acute trypanosoma brucei rhodesiense hat (rhat) has been expanding, driven by importation of infected cattle into regions previously free of the disease. these regions are also affected by african animal trypanosomiasis (aat) demanding a strategy for integrated disease control. | 2017 | 28162093 |
| kynurenine pathway activation in human african trypanosomiasis. | the kynurenine pathway of tryptophan oxidation is associated with cns inflammatory pathways. inhibition of this pathway ameliorates cns inflammation in rodent models of the late (meningoencephalitic) stage of human african trypanosomiasis (hat). in this study we evaluate whether the kynurenine pathway is activated in clinical hat and if it is associated with cns inflammatory responses. | 2016 | 28013248 |
| the relationship of endotoxaemia to peripheral and central nervous system inflammatory responses in human african trypanosomiasis. | endotoxaemia has been described in cases of human african trypanosomiasis (hat), but it is unclear if this phenomenon influences inflammatory pathology either in the periphery or central nervous system (cns). we studied endotoxin concentrations in the plasma and cerebrospinal fluid (csf) of trypanosoma brucei rhodesiense patients using the chromogenic limulus amoebocyte lysate assay. the relationship of endotoxin concentration to the presentation of gross signs of inflammation and the inflammato ... | 2017 | 27894360 |
| synthesis, dna binding and antitrypanosomal activity of benzimidazole analogues of dapi. | a series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). the new amidines were evaluated in vitro against the protozoan parasite trypanosoma brucei rhodesiense (t. b. r.). the thiophene analogue 5b and the n-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent i. | 2016 | 27843114 |
| quantifying heterogeneity in host-vector contact: tsetse (glossina swynnertoni and g. pallidipes) host choice in serengeti national park, tanzania. | identifying hosts of blood-feeding insect vectors is crucial in understanding their role in disease transmission. rhodesian human african trypanosomiasis (rhat), also known as acute sleeping sickness is caused by trypanosoma brucei rhodesiense and transmitted by tsetse flies. the disease is commonly associated with wilderness areas of east and southern africa. such areas hold a diverse range of species which form communities of hosts for disease maintenance. the relative importance of different ... | 2016 | 27706167 |
| a primate apol1 variant that kills trypanosoma brucei gambiense. | humans are protected against infection from most african trypanosomes by lipoprotein complexes present in serum that contain the trypanolytic pore-forming protein, apolipoprotein l1 (apol1). the human-infective trypanosomes, trypanosoma brucei rhodesiense in east africa and t. b. gambiense in west africa have separately evolved mechanisms that allow them to resist apol1-mediated lysis and cause human african trypanosomiasis, or sleeping sickness, in man. recently, apol1 variants were identified ... | 2016 | 27494254 |
| 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 |
| population genetic structure and temporal stability among trypanosoma brucei rhodesiense isolates in uganda. | the population structure and role of genetic exchange in african trypanosomes have been previously analyzed albeit with contradictory findings. to further investigate the role of genetic polymorphism on the population genetic structure of trypanosoma b. rhodesiense, we hypothesized that parasite genotypes are clonal and stable over time. | 2016 | 27142001 |
| synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against trypanosoma brucei rhodesiense. | 2-(2-benzamido)ethyl-4-phenylthiazole (1) was one of 1035 molecules (grouped into 115 distinct scaffolds) found to be inhibitory to trypanosoma brucei, the pathogen causing human african trypanosomiasis, at concentrations below 3.6μm and non-toxic to mammalian (huh7) cells in a phenotypic high-throughput screen of a 700,000 compound library performed by the genomics institute of the novartis research foundation (gnf). compound 1 and 72 analogues were synthesized in this lab by one of two general ... | 2016 | 27102161 |
| apolipoprotein l1 variant associated with increased susceptibility to trypanosome infection. | african trypanosomes, except trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, which cause human african trypanosomiasis, are lysed by the human serum protein apolipoprotein l1 (apol1). these two subspecies can resist human apol1 because they express the serum resistance proteins t. b. gambiense glycoprotein (tgsgp) and serum resistance-associated protein (sra), respectively. whereas in t. b. rhodesiense, sra is necessary and sufficient to inhibit apol1, in t. b. gambiense, tgsgp ... | 2016 | 27073096 |
| 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 ... | 2015 | 27053915 |
| comparative genomics of drug resistance in trypanosoma brucei rhodesiense. | trypanosoma brucei rhodesiense is one of the causative agents of human sleeping sickness, a fatal disease that is transmitted by tsetse flies and restricted to sub-saharan africa. here we investigate two independent lines of t. b. rhodesiense that have been selected with the drugs melarsoprol and pentamidine over the course of 2 years, until they exhibited stable cross-resistance to an unprecedented degree. we apply comparative genomics and transcriptomics to identify the underlying mutations. o ... | 2016 | 26973180 |
| structural characterization of the c-terminal coiled-coil domains of wild-type and kidney disease-associated mutants of apolipoprotein l1. | trypanosomes that cause sleeping sickness endocytose apolipoprotein l1 (apol1)-containing trypanolytic factors from human serum, leading to trypanolytic death through generation of apol1-associated lytic pores in trypanosomal membranes. the trypanosome trypanosoma brucei rhodesiense counteracts trypanolysis by expressing the surface protein serum response-associated (sra), which can bind apol1 common variant g0 to block its trypanolytic activity. however, two missense variants in the c terminal ... | 2016 | 26945671 |
| 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 |
| the role of cytokines in the pathogenesis and staging of trypanosoma brucei rhodesiense sleeping sickness. | human african trypanosomiasis due to trypanosoma brucei rhodesiense is invariably fatal if untreated with up to 12.3 million people at a risk of developing the disease in sub-saharan africa. the disease is characterized by a wide spectrum of clinical presentation coupled with differences in disease progression and severity. while the factors determining this varied response have not been clearly characterized, inflammatory cytokines have been partially implicated as key players. in this review, ... | 2016 | 26807135 |
| development of resazurin-based assay in 384-well format for high throughput whole cell screening of trypanosoma brucei rhodesiense strain stib 900 for the identification of potential anti-trypanosomal agents. | to accelerate the discovery of novel leads for the treatment of human african trypanosomiasis (hat), it is necessary to have a simple, robust and cost-effective assay to identify positive hits by high throughput whole cell screening. most of the fluorescence assay was made in black plate however in this study the hts assay developed in 384-well format using clear plate and black plate, for comparison. the hts assay developed is simple, sensitive, reliable and reproducible in both types of plates ... | 2016 | 26772786 |
| 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. | 2015 | 26715446 |
| design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-trifluorobenzothiophenes. | current treatments for human african trypanosomiasis (hat) are limited in their application, have undesirable dosing regimens and unsatisfactory toxicities highlighting the need for the development of a safer drug pipeline. our medicinal chemistry programme in developing rapidly accessible and modifiable heterocyclic scaffolds led to the design and synthesis of novel substituted benzothiophenes, with 6-benzimidazol-1-ylbenzothiophene derivatives demonstrating significant antitrypanosomal activit ... | 2016 | 26698538 |
| development of multiplex serological assay for the detection of human african trypanosomiasis. | human african trypanosomiasis (hat) is a disease caused by kinetoplastid infection. serological tests are useful for epidemiological surveillance. the aim of this study was to develop a multiplex serological assay for hat to assess the diagnostic value of selected hat antigens for sero-epidemiological surveillance. we cloned loci encoding eight antigens from trypanosoma brucei gambiense, expressed the genes in bacterial systems, and purified the resulting proteins. antigens were subjected to lum ... | 2016 | 26519611 |
| 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 ... | 2015 | 26505639 |
| 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 ... | 2015 | 26381210 |
| 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 ... | 2015 | 26342866 |
| 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 ... | 2015 | 26306311 |
| 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 |
| 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 |
| 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- ... | 2015 | 26099681 |
| 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. | 2015 | 26090964 |
| 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 ... | 2015 | 25953023 |
| 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 |
| 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 ... | 2015 | 25786994 |
| 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 ... | 2015 | 25740635 |
| 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 ... | 2015 | 25719539 |
| 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 ... | 2015 | 25656360 |
| 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 ... | 2015 | 25611014 |
| apol1 nephropathy: from gene to mechanisms of kidney injury. | the contribution of african ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein l1 (apol1). the apol1 variants appear at a high allele frequency in populations of west african ancestry as a result of apparent adaptive selection of the heterozygous state. heterozygosity protects from infection with trypanosoma brucei rhodesiense. this review will describe the ... | 2016 | 25561578 |
| 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 ... | 2014 | 25532828 |
| 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 ... | 2015 | 25479093 |
| 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 ... | 2014 | 25426112 |
| 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 |
| 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 ... | 2014 | 25125985 |
| 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 |
| 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 ... | 2014 | 24975321 |
| 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 |
| 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 ... | 2014 | 24808134 |
| 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. | 2014 | 24789741 |
| 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 ... | 2014 | 24776813 |
| 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 ... | 2014 | 24584715 |
| 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. | 2014 | 24529084 |
| 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. | 2013 | 24499540 |