| synthesis and in vitro antiprotozoal activities of dicationic 3,5-diphenylisoxazoles. | 3,5-bis(4-amidinophenyl)isoxazole (3)-an analogue of 2,5-bis(4-amidinophenyl)furan (furamidine) in which the central furan ring is replaced by isoxazole-and 42 novel analogues were prepared by two general synthetic pathways. the 43 isoxazole derivatives were assayed against trypanosoma brucei rhodesiense (t. brucei rhodesiense) stib900, plasmodium falciparum (p. falciparum) k1, and rat myoblast l6 cells (for cytotoxicity) in vitro. eleven compounds (3, 13, 16-18, 22, 26, 29, 31, 37, and 41) exhi ... | 2007 | 17439202 |
| resolution of the species problem in african trypanosomes. | there is a general assumption that eukaryote species are demarcated by morphological or genetic discontinuities. this stems from the idea that species are defined by the ability of individuals to mate and produce viable progeny. at the microscopic level, where organisms often proliferate more by asexual than sexual reproduction, this tidy classification system breaks down and species definition becomes messy and problematic. the dearth of morphological characters to distinguish microbial species ... | 2007 | 17451719 |
| characterisation of the trypanosoma brucei rhodesiense isolates from tanzania using serum resistance associated gene as molecular marker. | serum resistance associated (sra) gene has been found to confer resistance to the innate trypanolytic factor (tlf) found in normal human serum; thus allowing trypanosoma brucei brucei to survive exposure to normal human serum. this study was carried out to examine the presence of sra gene and identify the origin of t. b. rhodesiense isolates from three districts in tanzania, namely kibondo, kasulu and urambo. twenty-six t. b. rhodesiense isolates and two references t. b. rhodesiense isolates fro ... | 2007 | 17547097 |
| targeting the polyamine biosynthetic enzymes: a promising approach to therapy of african sleeping sickness, chagas' disease, and leishmaniasis. | trypanosomatids depend on spermidine for growth and survival. consequently, enzymes involved in spermidine synthesis and utilization, i.e. arginase, ornithine decarboxylase (odc), s-adenosylmethionine decarboxylase (adometdc), spermidine synthase, trypanothione synthetase (trys), and trypanothione reductase (tryr), are promising targets for drug development. the odc inhibitor alpha-difluoromethylornithine (dfmo) is about to become a first-line drug against human late-stage gambiense sleeping sic ... | 2007 | 17610127 |
| african trypanosomiasis in a british soldier. | sleeping sickness (human african trypanosomiasis) is a parasitic infection transmitted by day-biting tsetse flies. the diagnostic standard is microscopy of blood, lymph node aspirates, or cerebrospinal fluid. the disease is invariably fatal if not treated. there are >300,000 new cases of sleeping sickness each year and approximately 100,000 deaths. | 2007 | 17691692 |
| evaluation of antiprotozoal and antimycobacterial activities of the resin glycosides and the other metabolites of scrophularia cryptophila. | resin glycosides are secondary metabolites exclusive to the convolvulaceous plants. in this study, crypthophilic acids a-c (1-3), the first resin glycosides occurring in another family (scrophulariaceae), and the other constituents of scrophularia cryptophila were examined for in vitro antiprotozoal and antimycobacterial potentials. except for crypthophilic acid b (2), all tested compounds exhibited growth-inhibitory effect against trypanosoma brucei rhodesiense, with l-tryptophan (6) and buddle ... | 2008 | 17761408 |
| novel trypanocidal analogs of 5'-(methylthio)-adenosine. | the purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (heta) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (mta). heta is a lead structure for the ongoing development of selectively targeted trypanocidal agents. thirteen novel heta analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of trypanosoma brucei brucei lab 110 eatro and at least one drug-resistant trypanosoma brucei rhodesiense clinical ... | 2008 | 17954686 |
| synthesis and antiprotozoal activity of novel bis-benzamidino imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines. | the key dinitrile intermediates 4a-d were synthesized by reaction of phenacyl bromide 1 and the appropriate 2-amino-5-bromopyridines to yield 3a-d. suzuki coupling of 3a-d with 4-cyanophenylboronic acid yielded the 2,6-bis(4-cyanophenyl)-imidazo[1,2-a]pyridine derivatives 4a-d. the bis-amidoximes 5a-d, obtained from 4a-d by the action of hydroxylamine, were converted to the bis-o-acetoxyamidoximes which on catalytic hydrogenation in a mixture of ethanol/ethyl acetate gave the acetate salts of 2, ... | 2008 | 17976993 |
| spatially and genetically distinct african trypanosome virulence variants defined by host interferon-gamma response. | we describe 2 spatially distinct foci of human african trypanosomiasis in eastern uganda. the tororo and soroti foci of trypanosoma brucei rhodesiense infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. in particular, infections with the tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage a ... | 2007 | 18008245 |
| loop-mediated isothermal amplification (lamp) method for rapid detection of trypanosoma brucei rhodesiense. | loop-mediated isothermal amplification (lamp) of dna is a novel technique that rapidly amplifies target dna under isothermal conditions. in the present study, a lamp test was designed from the serum resistance-associated (sra) gene of trypanosoma brucei rhodesiense, the cause of the acute form of african sleeping sickness, and used to detect parasite dna from processed and heat-treated infected blood samples. the sra gene is specific to t. b. rhodesiense and has been shown to confer resistance t ... | 2008 | 18253475 |
| infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure. | the parasite trypanosoma brucei rhodesiense and its insect vector glossina morsitans morsitans were used to evaluate the effect of parasite clearance (resistance) as well as the cost of midgut infections on tsetse host fitness. tsetse flies are viviparous and have a low reproductive capacity, giving birth to only 6-8 progeny during their lifetime. thus, small perturbations to their reproductive fitness can have a major impact on population densities. we measured the fecundity (number of larval p ... | 2008 | 18335067 |
| synthesis of a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives bearing anti-trypanosomal and anti-leishmanial activity. | taking advantage of the structural features of natural products showing anti-trypanosomatid activity, we designed and synthesized a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives. the library was obtained following a parallel approach and using readily available synthons. all the derivatives showed inhibitory activity toward either trypanosoma or leishmania species, with 8, 10, and 16 being the most active compounds against trypanosoma brucei rhodesiens ... | 2008 | 18353643 |
| novel bisbenzimidazoles with antileishmanial effectiveness. | a small library of 2,2'-[(alpha,omega-alkanediylbis(oxyphenylene)]bis-1h-benzimidazoles has been prepared and screened in vitro against pneumocystis carinii, trypanosoma brucei rhodesiense, and leishmania donovani. among the six tested compounds two derivatives emerged as promising hits characterized by ic(50) values lower than that determined for pentamidine against l. donovani. | 2008 | 18367395 |
| high levels of genetic differentiation between ugandan glossina fuscipes fuscipes populations separated by lake kyoga. | glossina fuscipes fuscipes is the major vector of human african trypanosomiasis, commonly referred to as sleeping sickness, in uganda. in western and eastern africa, the disease has distinct clinical manifestations and is caused by two different parasites: trypanosoma brucei rhodesiense and t. b. gambiense. uganda is exceptional in that it harbors both parasites, which are separated by a narrow 160-km belt. this separation is puzzling considering there are no restrictions on the movement of peop ... | 2008 | 18509474 |
| genetic analysis of the human infective trypanosome trypanosoma brucei gambiense: chromosomal segregation, crossing over, and the construction of a genetic map. | trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-saharan africa, and it has been subdivided into three subspecies: trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, which cause sleeping sickness in humans, and the nonhuman infective trypanosoma brucei brucei. t. b. gambiense is the most clinically relevant subspecies, being responsible for more than 90% of all trypanosomal disease in humans. the genome sequence is now available ... | 2008 | 18570680 |
| synthesis of bicyclic amines and their activities against trypanosoma brucei rhodesiense and plasmodium falciparum k1. | new alkenes, aziridines, and diamines were prepared from antiprotozoal 4-dialkylaminobicyclo[2.2.2]octan-2-imines to investigate the influence of several functional groups in position 2 of the ring skeleton on the antitrypanosomal and antiplasmodial activities. they were synthesized from 4-dialkylaminobicyclo[2.2.2]octan-2-imines and tested for their activities against trypanosoma b. rhodesiense and plasmodium falciparum k1 (resistant to chloroquine and pyrimethamine) using in vitro microplate a ... | 2008 | 18563349 |
| novel azabicyclo[3.2.2]nonane derivatives and their activities against plasmodium falciparum k1 and trypanosoma brucei rhodesiense. | new diaryl substituted 2-azabicyclo[3.2.2]nonane derivatives have been synthesized in order to investigate the influence of the aromatic substitution and of n substitution on the antiprotozoal activities of those compounds. following a manual method for the hansch approach, different 4-substituted aryl rings were systematically inserted, and moieties with varying basicity and polarity were attached to the ring nitrogen. all compounds were investigated for their activities against trypanosoma bru ... | 2008 | 18502136 |
| synthesis and in vitro antiprotozoal activities of water-soluble, inexpensive 3,7-bis(dialkylamino)phenoxazin-5-ium derivatives. | 3,7-bis(dialkylamino)phenoxazinium salts were synthesized and evaluated for in vitro activities against plasmodium falciparum, trypanosoma cruzi, t. brucei rhodesiense, and leishmania donovani. notably, the compounds showed potent antiprotozoal activities, especially against p. falciparum and t. cruzi. the compounds with alkyl side chains less than three carbons in length possessed good activities with high selective indices. | 2008 | 18476684 |
| novel linear triaryl guanidines, n-substituted guanidines and potential prodrugs as antiprotozoal agents. | a series of triaryl guanidines and n-substituted guanidines designed to target the minor groove of dna were synthesized and evaluated as antiprotozoal agents. selected carbamate prodrugs of these guanidines were assayed for their oral efficacy. the linear triaryl bis-guanidines 6a,b were prepared from their corresponding diamines 4a,b through the intermediate boc protected bis-guanidines 5a,b followed by acid catalyzed deprotection. the n-substituted guanidino analogues 9c-f were obtained in thr ... | 2008 | 18455271 |
| estimating the burden of rhodesiense sleeping sickness during an outbreak in serere, eastern uganda. | zoonotic sleeping sickness, or hat (human african trypanosomiasis), caused by infection with trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. previous assessments of the disease burden expressed as disability-adjusted life years (dalys) for this infection have not distinguished t.b. rhodesiense from infection with the related, but clinically distinct trypanosoma brucei gambiense form. t.b. rhodesiense occurs focally, and it is important to assess the burden at ... | 2008 | 18366755 |
| eliminating human african trypanosomiasis: where do we stand and what comes next? | | 2008 | 18303943 |
| new bis(2-aminoimidazoline) and bisguanidine dna minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity. | a series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against trypanosoma brucei rhodesiense stib900 and plasmodium falciparum k1. the dicationic diphenyl compounds exhibited the best activities with ic 50 values against t. b. rhodesiense and p. falciparum in the nanomolar range. five compounds (7b, 9a, 9b, 10b, and 14b) cured 100% of treated mice upon ip administration at 20 mg/kg in the difficult to cure t. b. rhodesiense stib900 mouse model. overall, the com ... | 2008 | 18247550 |
| african trypanosomiasis: sensitive and rapid detection of the sub-genus trypanozoon by loop-mediated isothermal amplification (lamp) of parasite dna. | control of human african trypanosomiasis (hat) is dependent on accurate diagnosis and treatment of infected patients. however, sensitivities of tests in routine use are unsatisfactory, due to the characteristically low parasitaemias in naturally infected individuals. we have identified a conserved sequence in the repetitive insertion mobile element (rime) of the sub-genus trypanozoon and used it to design primers for a highly specific loop-mediated isothermal amplification (lamp) test. the test ... | 2008 | 17991469 |
| [the controversial story of the human trypanolytic factor]. | | 2008 | 18950568 |
| synthesis and in vitro antiprotozoal activity of bisbenzofuran cations. | forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with alpha-halogenated ketones followed by intramolecular ring closure or by a copper- or palladium-mediated heteroannulation of substituted o-iodophenols with terminal acetylenes. in vitro antiprotozoal activities of compounds 1-43 against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani and cytotoxicity against mammalian cells were influenced by the position and the ty ... | 2007 | 17948982 |
| synthesis and in vitro protozoocidal evaluation of novel diazabicyclic tropolone derivatives. | the synthesis and in vitro antiparasitic activity of twenty-seven novel diazabicycles based on tropolone ethers is presented. the compounds can be readily prepared by means of a high-yielding hetero diels-alder reaction using simple and readily available starting materials. several of the new diazabicycles have in vitro activities against trypanosoma cruzi, leishmania donovani, trypanosoma brucei rhodesiense, and chloroquine-resistant plasmodium falciparum that are comparable or superior to thos ... | 2007 | 17924365 |
| antiprotozoal polyacetylenes from the tanzanian medicinal plant cussonia zimmermannii. | from the petroleum ether extract of the root bark of cussonia zimmermannii four polyacetylenes, 1- 4, were isolated, three of which ( 1- 3) were active against trypanosoma brucei rhodesiense, trypanosoma cruzi, plasmodium falciparum, and leishmania donovani. | 2007 | 17922552 |
| trypanocidal activity of piperazine-linked bisbenzamidines and bisbenzamidoxime, an orally active prodrug. | a series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of trypanosoma brucei brucei and a drug-resistant strain of trypanosoma brucei rhodesiense. the compounds showed similar potencies against both strains. the most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (ic(50))=1.7-3.0 nm) or c ... | 2007 | 17920820 |
| in vitro and in vivo evaluation of the antitrypanosomal activity of fractions of holarrhena africana. | the aqueous extract of young leaves of holarrhena africana, a plant used in the nigerian traditional medicine, exhibited good activity against trypanosoma brucei spp. the extract was fractionated and eight fractions were obtained. one fraction designated as haf(5) showed in vitro activity against trypanosoma brucei rhodesiense with an ic(50) value of 0.785 microg/mg and no overt cytotoxicity against l-6 cells. fraction haf(5) was tested in vivo at two doses and found to exhibit in vivo efficacy ... | 2007 | 17728085 |
| occurrence of multiple drug resistance in trypanosoma brucei rhodesiense isolated from sleeping sickness patients. | the occurrence of cross-resistance among melarsoprol-resistant trypanosoma brucei rhodesiense isolates was investigated in this study. the isolates, t. b. rhodesiense ketri 237, 2538, 1992, 2709, 2694 and 3530, had been obtained from sleeping sickness patients in kenya and uganda between 1960 and 1985. five groups consisting of six mice each were inoculated intraperitoneally with 10(5) parasites of each isolate, and 24 h later treated with either melarsoprol, homidium chloride, diminazene acetur ... | 2007 | 17708149 |
| efficacy of the novel diamidine compound 2,5-bis(4-amidinophenyl)- furan-bis-o-methlylamidoxime (pafuramidine, db289) against trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration. | owing to the lack of oral drugs for human african trypanosomiasis, patients have to be hospitalized for 10 to 30 days to facilitate treatment with parenterally administered medicines. the efficacy of a novel orally administered prodrug, 2,5-bis(4-amidinophenyl)-furan-bis-o-methlylamidoxime (pafuramidine, db289), was tested in the vervet monkey (chlorocebus [cercopithecus] aethiops) model of sleeping sickness. five groups of three animals each were infected intravenously with 10(4) trypanosoma br ... | 2009 | 19064893 |
| 2,n6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities. | a library of 2,n(6)-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. it was found that 2-methoxy and 2-histamino and n(6)-m-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. the best antiplasmodial activity was achieved with large aromatic substitutions, such as n(6)-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the ... | 2007 | 17698622 |
| aggravation of pathogenesis mediated by ochratoxin a in mice infected with trypanosoma brucei rhodesiense. | mice fed 1.5 mg ochratoxin a (ota) per kg body weight and infected with trypanosoma brucei rhodesiense were compared with trypanosome-infected placebo-fed and uninfected ota-fed controls. uninfected ota-fed mice showed fever, lethargy, facial and eyelid oedemas, mild hepatitis and nephritis, and high survival. infected placebo-fed controls had mean pre-patent period (ppp) of 3.26 days, lethargy, dyspnoea, fever, facial and scrotal oedema, survival of 33-65 days, reduced red cell counts (rcc: 10. ... | 2009 | 19154650 |
| epimers of bicyclo[2.2.2]octan-2-ol derivatives with antiprotozoal activity. | (2sr,6rs,7rs)-4-dialkylaminobicyclo[2.2.2]octan-2-ols and several of their esters have shown promising activity against the causative organisms for malaria and sleeping sickness. the base-catalyzed epimerization of the alcohols was carried out by different methods giving their (2rs,6rs,7rs)-isomers. best results were obtained by the consecutive use of potassium tert-butoxide and sodium. the isomeric alcohols were converted to selected esters. all new compounds were tested for their activity agai ... | 2008 | 17698258 |
| anti-african trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic analogues. | the known anti-protozoal activity of flavonoids has stimulated the testing of other derivatives from natural and synthetic sources. | 2009 | 19178775 |
| a multiplex pcr that discriminates between trypanosoma brucei brucei and zoonotic t. b. rhodesiense. | two subspecies of trypanosoma brucei s.l. co-exist within the animal populations of eastern africa; t. b. brucei a parasite which only infects livestock and wildlife and t. b. rhodesiense a zoonotic parasite which infects domestic livestock, wildlife, and which in humans, results in the disease known as human african trypanosomiasis (hat) or sleeping sickness. in order to assess the risk posed to humans from hat it is necessary to identify animals harbouring potentially human infective parasites ... | 2008 | 17643434 |
| human african trypanosomiasis: pharmacological re-engagement with a neglected disease. | this review discusses the challenges of chemotherapy for human african trypanosomiasis (hat). the few drugs registered for use against the disease are unsatisfactory for a number of reasons. hat has two stages. in stage 1 the parasites proliferate in the haemolymphatic system. in stage 2 they invade the central nervous system and brain provoking progressive neurological dysfunction leading to symptoms that include the disrupted sleep wake patterns that give hat its more common name of sleeping s ... | 2007 | 17618313 |
| melarsoprol- and pentamidine-resistant trypanosoma brucei rhodesiense populations and their cross-resistance. | resistance to melarsoprol and pentamidine was induced in bloodstream-form trypanosoma brucei rhodesiense stib 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. the resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. after proliferation in the mouse, trypanosomes were isolated and their ic(50) values to the three drugs were de ... | 2007 | 17602691 |
| the soluble variant surface glycoprotein of african trypanosomes is recognized by a macrophage scavenger receptor and induces i kappa b alpha degradation independently of traf6-mediated tlr signaling. | the gpi residues of soluble variant surface glycoprotein (svsg) molecules released from the membrane of african trypanosomes during infection induce macrophage activation events. in this study, we demonstrate that the trypanosome svsg molecule binds to the membrane of murine raw 264.7 macrophages and activates the nf-kappab cascade independently of a tlr-mediated interaction. the binding of fluorochrome-labeled svsg molecules to macrophage membranes was saturable, was inhibited by the scavenger ... | 2007 | 17579076 |
| bicyclo[2.2.2]octyl esters of dialkylamino acids as antiprotozoals. | a couple of bicyclo[2.2.2]octyl esters of 2-dialkylaminoacetic acids were prepared. their antiplasmodial and antitrypanosomal activities against trypanosoma brucei rhodesiense (stib 900) and the k(1) strain of plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. structure-activity relationships were discussed. the antiprotozoal activities were remarkably increased by insertion of a second basic centre. the selectivity indices of the most act ... | 2007 | 17544672 |
| novel s-adenosylmethionine decarboxylase inhibitors for the treatment of human african trypanosomiasis. | trypanosomiasis remains a significant disease across the sub-saharan african continent, with 50,000 to 70,000 individuals infected. the utility of current therapies is limited by issues of toxicity and the need to administer compounds intravenously. we have begun a program to pursue lead optimization around mdl 73811, an irreversible inhibitor of s-adenosylmethionine decarboxylase (adometdc). this compound is potent but in previous studies cleared rapidly from the blood of rats (t. l. byers, t. ... | 2009 | 19289530 |
| diphenyl furans and aza analogs: effects of structural modification on in vitro activity, dna binding, and accumulation and distribution in trypanosomes. | human african trypanosomiasis is a devastating disease with only a few treatment options, including pentamidine. diamidine compounds such as pentamidine, db75, and db820 are potent antitrypanosomal compounds. previous investigations have shown that diamidines accumulate to high concentrations in trypanosomes. however, the mechanism of action of this class of compounds remains unknown. a long-hypothesized mechanism of action has been binding to dna and interference with dna-associated enzymes. th ... | 2007 | 17517831 |
| public-private partnership works to stamp out sleeping sickness in uganda. | | 2007 | 17392023 |
| chemotherapeutic strategies against trypanosoma brucei: drug targets vs. drug targeting. | trypanosoma brucei rhodesiense and t. b. gambiense are the causative agents of sleeping sickness, a fatal disease that affects 36 countries in sub-saharan africa. nevertheless, only a handful of clinically useful drugs are available. these drugs suffer from severe side-effects. the situation is further aggravated by the alarming incidence of treatment failures in several sleeping sickness foci, apparently indicating the occurrence of drug-resistant trypanosomes. because of these reasons, and sin ... | 2007 | 17346174 |
| antiplasmodial and antitrypanosomal activities of aminobicyclo[2.2.2]octyl omega-aminoalkanoates. | several 4-aminobicyclo[2.2.2]octyl esters of omega-dialkylamino acids were prepared. their activities against the multidrug-resistant k(1) strain of plasmodium falciparum and trypanosoma brucei rhodesiense (stib 900) were determined using microplate assays and compared to those of formerly prepared analogues. the biological activity was influenced by the relative configuration in ring position 2, by the chain length of the acid moiety and by the amino substitution. the most active antiplasmodial ... | 2009 | 18571774 |
| in vitro and in vivo antitrypanosomal activities of three peptide antibiotics: leucinostatin a and b, alamethicin i and tsushimycin. | in the course of our screening for antitrypanosomal compounds from soil microorganisms, as well as from the antibiotics library of the kitasato institute for life sciences, we found three peptide antibiotics, leucinostatin (a and b), alamethicin i and tsushimycin, which exhibited potent or moderate antitrypanosomal activity. we report here the in vitro and in vivo antitrypanosomal properties and cytotoxicities of leucinostatin a and b, alamethicin i and tsushimycin compared with suramin. we also ... | 2009 | 19407848 |
| synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes, bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes. | a series of 37 dicationically substituted bis(phenoxymethyl)benzene bis(phenoxymethyl)naphthalene, and bis(benzyloxy)naphthalene analogues of pentamidine was prepared and evaluated for antiprotozoal activities and cytotoxicity in in vitro. 1,3-bis(4-amidinophenoxymethyl)benzene (1) was the most active against trypanosoma brucei rhodesiense (ic(50)=2.1 nm). 1,3-bis[4-(n-isopropylamidino)phenoxymethyl]benzene (2) was most active against plasmodium falciparum (ic(50)=3.6 nm) and displayed a selecti ... | 2009 | 19409677 |
| analysis of risk factors for t. brucei rhodesiense sleeping sickness within villages in south-east uganda. | sleeping sickness (hat) caused by t.b. rhodesiense is a major veterinary and human public health problem in uganda. previous studies have investigated spatial risk factors for t.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. in the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for hat in an endemic area. | 2008 | 18590541 |
| trypanocidal activity of 8-methyl-5'-{[(z)-4-aminobut-2-enyl]-(methylamino)}adenosine (genz-644131), an adenosylmethionine decarboxylase inhibitor. | genzyme 644131, 8-methyl-5'-{[(z)-4-aminobut-2-enyl](methylamino)}adenosine, is an analog of the enzyme activated s-adenosylmethionine decarboxylase (adometdc) inhibitor and the trypanocidal agent mdl-7381, 5-{[(z)-4-aminobut-2-enyl](methylamino)}adenosine. the analog differs from the parent in having an 8-methyl group on the purine ring that bestows favorable pharmacokinetic, biochemical, and trypanocidal activities. the compound was curative in acute trypanosoma brucei brucei and drug-resistan ... | 2009 | 19451291 |
| parallel synthesis of a series of non-functional atp/nad analogs with activity against trypanosomatid parasites. | non-functional analogs of the cofactors atp and nad are putative inhibitors of atp- or nad-dependant enzymes. since pathogenic protozoa rely heavily on the salvage of purine nucleosides from the bloodstream of their host, such compounds are of interest as antiplasmodial and antitrypanosomal agents with a multitude of molecular targets. by replacing the negatively charged phosphate residues with a constrained unsaturated amide spacer and the nicotinamide moiety of nad with various lipophilic subs ... | 2010 | 19484371 |
| quantitative structure--antiprotozoal activity relationships of sesquiterpene lactones. | prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (stls) against trypanosoma brucei rhodesiense (which causes east african sleeping sickness), we have now conducted a structure-(in-vitro)-activity study on a set of 40 stls against t. brucei rhodesiense, t. cruzi, leishmania donovani and plasmodium falciparum. furthermore, cytotoxic activity against l6 rat skeletal myoblast cells was assessed. some of the compounds possess high activity, espec ... | 2009 | 19513006 |
| antiprotozoal activity of 1-phenethyl-4-aminopiperidine derivatives. | a series of 44 4-aminopiperidine derivatives was screened in vitro against four protozoan parasites (trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum). this screening identified 29 molecules selectively active against bloodstream-form t. b. rhodesiense trypomastigotes, with 50% inhibitory concentrations (ic50) ranging from 0.12 to 10 microm, and 33 compounds active against the chloroquine- and pyrimethamine-resistant k1 strain of p. falciparum (ic ... | 2009 | 19564359 |
| immunospecific immunoglobulins and il-10 as markers for trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys. | to determine the usefulness of il-10 and immunoglobulin m (igm) as biomarkers for staging hat in vervet monkeys, a useful pathogenesis model for humans. | 2009 | 19573160 |
| the trypanosoma brucei flagellum: moving parasites in new directions. | african trypanosomes are devastating human and animal pathogens. trypanosoma brucei rhodesiense and t. b. gambiense subspecies cause the fatal human disease known as african sleeping sickness. it is estimated that several hundred thousand new infections occur annually and the disease is fatal if untreated. t. brucei is transmitted by the tsetse fly and alternates between bloodstream-form and insect-form life cycle stages that are adapted to survive in the mammalian host and the insect vector, re ... | 2009 | 19575562 |
| synthesis and antiprotozoal activity of pyridyl analogues of pentamidine. | a series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani, and for cytotoxicity against mammalian cells. antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. diamidine 6 with cationic m ... | 2009 | 19606902 |
| new treatment option for second-stage african sleeping sickness: in vitro and in vivo efficacy of aza analogs of db289. | african sleeping sickness is a fatal parasitic disease, and all drugs currently in use for treatment have strong liabilities. it is essential to find new, effective, and less toxic drugs, ideally with oral application, to control the disease. in this study, the aromatic diamidine db75 (furamidine) and two aza analogs, db820 and db829 (cpd-0801), as well as their methoxyamidine prodrugs and amidoxime metabolites, were evaluated against african trypanosomes. the active parent diamidines showed sim ... | 2009 | 19620327 |
| mutual self-defence: the trypanolytic factor story. | around 1900 laveran and mesnil discovered that african trypanosomes (prototype: trypanosoma brucei brucei) do not survive in the blood of some primates and humans. the nature of the trypanolytic factor present in these sera has been the focus of a long-standing debate between different groups, but recent developments have allowed the proposal of a coherent model incorporating most seemingly divergent views and providing an interesting example of the complex interplay that continuously occurs bet ... | 2008 | 18675374 |
| the continuing problem of human african trypanosomiasis (sleeping sickness). | human african trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub-saharan africa. transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus trypanosoma and comes in two types: east african human african trypanosomiasis caused by trypanosoma brucei rhodesiense and the west african form caused by trypanosoma brucei gambiense. there is an early or hemo ... | 2008 | 18756506 |
| controlling sleeping sickness - a review. | following a period characterized by severe epidemics of sleeping sickness, restoration of effective control and surveillance systems has raised the question of eliminating the disease from sub-saharan africa. given sufficient political and financial support, elimination is now considered a reasonable aim in countries reporting zero or less than 100 cases per year. this success may lead health authorities across the affected region to downgrade the disease from 'neglected' to simply being ignored ... | 2009 | 19691861 |
| development of drug resistance in trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. treatment of human african trypanosomiasis with natural products (review). | human african trypanosomiasis is an infectious disease which has resulted in the deaths of thousands of people in sub-saharan africa. two subspecies of the protozoan parasite trypanosoma brucei are the causative agents of the infection, whereby t. b. gambiense leads to chronic development of the disease and t. b. rhodesiense establishes an acute form, which is fatal within months or even weeks. current chemotherapy treatment is complex, since special drugs have to be used for the different devel ... | 2008 | 18813846 |
| synthesis and antiprotozoal activity of cationic 2-phenylbenzofurans. | a series of cationically substituted 2-phenylbenzofurans 1- 49 have been synthesized, and their in vitro antiprotozoal properties against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani, as well as cytotoxicity against mammalian cells, have been evaluated. eight dications exhibited antitrypanosomal activities comparable to that of pentamidine and melarsoprol. twenty-six compounds were more active than pentamidine, and seven dications demonstrated increased activiti ... | 2008 | 18841956 |
| novel 2h-isoquinolin-3-ones as antiplasmodial falcipain-2 inhibitors. | a series of 1-aryl-6,7-disubstituted-2h-isoquinolin-3-ones (2-10) was synthesized and evaluated for their inhibition against plasmodium falciparum cysteine protease falcipain-2, as well as against cultured p. falciparum strain fcbr parasites. all compounds displayed inhibitory activity against recombinant falcipain-2 and against in vitro cultured intraerythrocytic p. falciparum, with the exception of 9. the new compounds exhibited no selectivity against human cysteine proteases such as cathepsin ... | 2009 | 19709887 |
| on-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences. | a new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. as target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (plasmodium falciparum) and african sleeping sickness (trypanosoma brucei rhodesiense). the best inhibitors with unusual amino acid sequences not reported before for thi ... | 2009 | 19715342 |
| trypanosoma brucei rhodesiense transmitted by a single tsetse fly bite in vervet monkeys as a model of human african trypanosomiasis. | we have investigated the pathogenicity of tsetse (glossina pallidipes)-transmitted cloned strains of trypanosoma brucei rhodesiense in vervet monkeys. tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the bite of a single infected fly. chancres developed in five of the nine (55.6%) monkeys within 4 to 8 days post infection (dpi). all nine individuals were successfully infected, with a median pre-patent period of 4 (rang ... | 2008 | 18846231 |
| diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities. | trypanothione reductase (tr) is an essential enzyme of trypanosomatids and therefore a promising target for the development of new drugs against african sleeping sickness and chagas' disease. diaryl sulfides with a central anilino moiety, decorated with a flexible n-alkyl side chain bearing a terminal ammonium ion, are a known class of inhibitors. using computer modelling, we revised the binding model for this class of tr inhibitors predicting simultaneous interactions of the ammonium ion-termin ... | 2008 | 18931800 |
| the epidemiology of trypanosomiasis in rumphi district, malawi: a ten year retrospective study. | human african trypanosomiasis (hat) is caused by two species of the tsetse fly vectored protozoan hemoflagellates belonging to trypanosma brucei, namely t.b gambiense which predominates in western africa and follows a chronic disease course and t.b rhodensiense which is more prevalent in southern and eastern africa, malawi included, and follows a more acute and aggressive disease course. previous studies in the democratic republic of congo, angola, uganda and sudan have demonstrated that the pre ... | 2009 | 19780474 |
| isolation of aerucyclamides c and d and structure revision of microcyclamide 7806a: heterocyclic ribosomal peptides from microcystis aeruginosa pcc 7806 and their antiparasite evaluation. | aerucyclamides c and d were isolated from the cyanobacterium microcystis aeruginosa pcc 7806, and their structures established by nmr spectroscopy and chemical transformation and degradation. acidic hydrolysis of aerucyclamide c (cf(3)co(2)h, h(2)o) resulted in microcyclamide 7806a. this chemical evidence combined with spectroscopic and physical data suggest a structure revision for microcyclamide 7806a, which incorporates an o-acylated thr ammonium residue instead of the originally proposed met ... | 2008 | 18973386 |
| synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds. | trypanothione reductase (tr) is a flavoenzyme unique to trypanosomatid parasites and a target for lead discovery programs. various inhibitor scaffolds have emerged in the past, exhibiting moderate affinity for the parasite enzyme. herein we show that the combination of two structural motifs of known tr inhibitors - diaryl sulfides and mepacrine - enables the simultaneous addressing of two hydrophobic patches in the active site. the binding efficacy of these conjugates is enhanced over that of th ... | 2009 | 19847846 |
| african trypanosomiasis in two short-term australian travelers to malawi. | we report two microbiologically confirmed cases of trypanosomiasis in short-term australian travelers to malawi. the initial diagnosis was followed by medi-evacuation to south africa where suramin therapy was commenced. the treatment course was completed on return to australia, with subsequent follow-up. this diagnosis should be considered in travelers returning from an endemic region. | 2008 | 19006517 |
| synthesis and antiparasitic and antifungal evaluation of 2'-arylsubstituted-1h,1'h-[2,5']bisbenzimidazolyl-5-carboxamidines. | a series of 2'-arylsubstituted-1h,1'h-[2,5']-bisbenzimidazolyl-5-carboxamidines were prepared in a six-step process starting from 4-amino-3-nitrobenzonitrile. the antiparasitic activity against trypanosoma brucei rhodesiense (t.b.r.), plasmodium falciparum (p.f.), leishmania donovani (l.d.) and trypanosoma cruzi (t.c.) and antifungal activity against candida albicans and candida krusei were evaluated in vitro. several compounds showed promising in vitro activity against t.b.r., p.f. and c. albic ... | 2009 | 19010569 |
| east african trypanosomiasis in a pregnant traveler. | | 2009 | 19891893 |
| traversal of human and animal trypanosomes across the blood-brain barrier. | the neurological complications of human african trypanosomiasis (hat) in man caused by the unicellular protozoan parasites trypanosoma brucei gambiense and t. b. rhodesiense are a consequence of the penetration of the blood-brain barrier (bbb) by trypanosomes that enter the central nervous system (cns). yet the mechanisms by which african trypanosomes cross the true bbb comprised of brain microvascular endothelial cells (bmecs) remain unclear. human bbb models used to determine how african trypa ... | 2008 | 19016378 |
| challenges in the diagnosis and management of sleeping sickness in tanzania: a case report. | in tanzania sleeping sickness presents a serious threat to human health with a country-wide average of 400 cases reported annually. both wild and domestic animals have been found to play a significant role in the epidemiology of sleeping sickness. serengeti national park in northern tanzania, has experienced a number of sleeping sickness epidemics since 1922. the epidemics were associated with abundant game animals in the areas and glossina swynnertoni was incriminated as the main vector. howeve ... | 2008 | 19024343 |
| antiprotozoal, antimycobacterial and cytotoxic potential of some british green algae. | in the continuation of our search for natural sources for antiprotozoal and antitubercular molecules, we have screened the crude extracts of four green marine algae (cladophora rupestris, codium fragile ssp. tomentosoides, ulva intestinalis and ulva lactuca) collected from the dorset area of england. trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and mycobacterium tuberculosis were used as test organisms in the in vitro assays. the selective toxicity of the extracts was a ... | 2010 | 19960429 |
| c-terminal mutants of apolipoprotein l-i efficiently kill both trypanosoma brucei brucei and trypanosoma brucei rhodesiense. | apolipoprotein l-i (apol1) is a human-specific serum protein that kills trypanosoma brucei through ionic pore formation in endosomal membranes of the parasite. the t. brucei subspecies rhodesiense and gambiense resist this lytic activity and can infect humans, causing sleeping sickness. in the case of t. b. rhodesiense, resistance to lysis involves interaction of the serum resistance-associated (sra) protein with the c-terminal helix of apol1. we undertook a mutational and deletional analysis of ... | 2009 | 19997494 |
| trypanosomiasis and the brain. | neurological involvement following trypanosome infection has been recognised for over a century. however, there are still many unanswered questions concerning the mechanisms used by the parasite to gain entry to the cns and the pathogenesis of the resulting neuroinflammatory reaction. there is a paucity of material from human cases of the disease therefore the majority of current research relies on the use of animal models of trypanosome infection. this review reports contemporary knowledge, fro ... | 2010 | 20028610 |
| characterization of trifluralin binding with recombinant tubulin from trypanosoma brucei. | the binding kinetics of five novel trifluralin analogs with recombinant alpha- and beta-tubulin proteins from trypanosoma brucei rhodesiense was determined. native tubulin from rats was used to determine the extent of binding of each analog to mammalian tubulin. the results of this study clearly demonstrate two important characteristics of the binding of these trifluralins to tubulin. firstly, they have specific affinity for trypanosomal tubulin compared with mammalian tubulin irrespective of th ... | 2009 | 19050925 |
| the burden of human african trypanosomiasis. | human african trypanosomiasis (hat, or sleeping sickness) is a protozoan parasitic infection caused by trypanosoma brucei rhodesiense or trypanosoma brucei gambiense. these are neglected tropical diseases, and t.b. rhodesiense hat is a zoonosis. we review current knowledge on the burden of hat in sub-saharan africa, with an emphasis on the disability-adjusted life year (daly), data sources, and methodological issues relating to the use of this metric for assessing the burden of this disease. we ... | 2008 | 19104653 |
| in vitro and in vivo antitrypanosomal activitiy of two microbial metabolites, ks-505a and alazopeptin. | our on-going screening program to discover new antitrypanosomal antibiotics has been evaluating compounds isolated from soil microorganisms as well as investigating the antibiotic libraries of the kitasato institute for life sciences and biofrontier laboratories of kyowa hakko kogyo co., ltd. we have now discovered two compounds, ks-505a and alazopeptin, which exhibit moderate antitrypanosomal characteristics. we report here the in vitro and in vivo antitrypanosomal activities and cytotoxicities ... | 2008 | 19168977 |
| trypanocidal, leishmanicidal and cytotoxic effects of anthecotulide-type linear sesquiterpene lactones from anthemis auriculata. | trypanosomiasis and leishmaniasis pose major public health threats for many countries, particularly those in sub-saharan africa and south america. in the present study, we evaluated the in vitro antiprotozoal activity of three irregular, linear sesquiterpene lactones recently isolated from greek anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3). trypomastigote forms of trypanosoma brucei rhodesiense and t. cruzi as well as axenic amastigotes ... | 2009 | 19200703 |
| antimalarial and antitubercular nostocarboline and eudistomin derivatives: synthesis, in vitro and in vivo biological evaluation. | the synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin n and o is reported. these compounds were evaluated in vitro against four parasites (trypanosoma brucei rhodesiense stib 900, trypanosoma cruzi tulahuen c2c4, leishmania donovani mhom-et-67/l82 axenic amastigotes, and plasmod ... | 2010 | 20133138 |
| isolation of secondary metabolites from hortia oreadica (rutaceae) leaves through high-speed counter-current chromatography. | high-speed counter-current chromatography (hsccc) with a two-phase solvent system (hexane-ethanol-acetonitrile-water 10:8:1:1, v/v) was applied to examine the leaves of hortia oreadica, which afforded the known limonoid guyanin (1), the alkaloids rutaecarpin (2) and dictamnine (6), the dihydrocinnamic acid derivatives methyl 5,7-dimethoxy-2,2-dimethyl-2h-1-benzopyran-6-propanoate (3), 5,8-dimethoxy-2,2-dimethyl-2h-1-benzopyran-6-propanoic acid (4), together with the new e-3,4-dimethoxy-alpha(3-h ... | 2009 | 19249788 |
| novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites. | human african trypanosomiasis (hat), caused by the protozoan parasite trypanosoma brucei spp., is a major health problem in sub-saharan africa. new drugs are urgently required for the disease. selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. for example, the p2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. we have previously reported the use o ... | 2009 | 19262935 |
| the antiprotozoal activity of methylated flavonoids from ageratum conyzoides l. | the dichloromethane extract prepared from aerial parts of ageratum conyzoides l. (asteraceae), a plant commonly used in folk medicine for a number of illnesses including sleeping sickness, was recently found to exhibit a prominent activity (ic(50)=0.78 microg/ml) against bloodstream forms of trypanosoma brucei rhodesiense, the etiologic agent of east african human trypanosomiasis (east african sleeping sickness). this extract also exhibited noticeable activities against leishmania donovani (kala ... | 2010 | 20219663 |
| a search for trypanosoma brucei rhodesiense diagnostic antigens by proteomic screening and targeted cloning. | the only available diagnostic method for east african trypanosomiasis is light microscopy of blood samples. a simple immunodiagnostic would greatly aid trypanosomiasis control. | 2010 | 20224787 |
| the modification of trypanosoma rhodesiense on prolonged syringe passage. | | 1947 | 20249287 |
| recommendations for control of east african sleeping sickness in uganda. | east african sleeping sickness, caused by trypanosoma brucei rhodesiense, is prominent in uganda and poses a serious public health challenge in the region. this publication attempts to provide key components for designing a strategy for a nationwide initiative to provide insecticide-treatment of the animal reservoir to control t. b. rhodesiense. the contents of this article will focus on insecticide-based vector control strategies, monitoring and evaluation framework, and knowledge gaps required ... | 2010 | 20300417 |
| biological variation among african trypanosomes: i. clonal expression of virulence is not linked to the variant surface glycoprotein or the variant surface glycoprotein gene telomeric expression site. | the potential association of variant surface glycoprotein (vsg) gene expression with clonal expression of virulence in african trypanosomes was addressed. two populations of clonally related trypanosomes, which differ dramatically in virulence for the infected host, but display the same apparent vsg surface coat phenotype, were characterized with respect to the vsg genes expressed as well as the chromosome telomeric expression sites (es) utilized for vsg gene transcription. the vsg gene sequence ... | 2010 | 20307190 |
| structure-activity study of pentamidine analogues as antiprotozoal agents. | diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani, and for cytotoxicity against mammalian cells. dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (ic(50) = 4 nm). nine congeners (2-4, 12, 27, 30, and 64-66) were more active against p. falciparum than artemisinin (ic(50) = 6 nm). eight compounds (12, 32, 33, 44 ... | 2009 | 19267462 |
| the antiprotozoal activity of sixteen asteraceae species native to sudan and bioactivity-guided isolation of xanthanolides from xanthium brasilicum. | in vitro screening of the dichloromethane extracts of 16 asteraceae species native to sudan for activity against major protozoan pathogens revealed that a xanthium brasilicum vell. [syn. x. strumarium var. brasilicum (vell.) baker in mart.] extract was the most active against trypanosoma brucei rhodesiense, the etiological agent of east african human trypanosomiasis (ic(50) = 0.1 microg/ml). this plant extract also exhibited noticeable activities against t. cruzi (chagas disease), leishmania don ... | 2009 | 19431098 |
| protease activated receptor signaling is required for african trypanosome traversal of human brain microvascular endothelial cells. | using human brain microvascular endothelial cells (hbmecs) as an in vitro model for how african trypanosomes cross the human blood-brain barrier (bbb) we recently reported that the parasites cross the bbb by generating calcium activation signals in hbmecs through the activity of parasite cysteine proteases, particularly cathepsin l (brucipain). in the current study, we examined the possible role of a class of protease stimulated hbmec g protein coupled receptors (gpcrs) known as protease activat ... | 2009 | 19621073 |
| identification of stage biomarkers for human african trypanosomiasis. | human african trypanosomiasis (hat), caused by infection with sub-species of trypanosoma brucei (t. b.), manifests as a hemolymphatic stage followed by an encephalitic stage. the distinction of the two stages needs improvement as drugs used for the late stage are highly toxic. transcripts encoding 16 secreted proteins differentially expressed in the brains of mice at late stage t. b. brucei infection when the early stage drug suramin is no longer effective and different to immunoglobulins, chemo ... | 2010 | 20519589 |
| processing and presentation of variant surface glycoprotein molecules to t cells in african trypanosomiasis. | th1 cell responses to the variant surface glycoprotein (vsg) of african trypanosomes play a critical role in controlling infection through the production of ifn-gamma, but the role of apcs in the induction and regulation of t cell-mediated protection is poorly understood. in this study, we have investigated the ag presentation capabilities of dendritic cells (dcs) and macrophages during early trypanosome infection in relatively resistant responder and susceptible nonresponder mouse strains. sple ... | 2009 | 19675169 |
| constrained peptidomimetics as antiplasmodial falcipain-2 inhibitors. | herein we report the synthesis of a series of novel constrained peptidomimetics 2-10 endowed with a dipeptide backbone (d-ser-gly) and a vinyl ester warhead, structurally related to a previously identified lead compound 1, an irreversible inhibitor of falcipain-2, the main haemoglobinase of lethal malaria parasite plasmodium falciparum. the new compounds were evaluated for their inhibition against falcipain-2, as well as against cultured p. falciparum. the inhibitory activity of the synthesized ... | 2010 | 20598553 |
| antiprotozoal steroidal saponins from the marine sponge pandaros acanthifolium. | the chemical composition of the caribbean sponge pandaros acanthifolium was reinvestigated and led to the isolation of 12 new steroidal glycosides, namely, pandarosides e-j (1-6) and their methyl esters (7-12). their structures were determined on the basis of extensive spectroscopic analyses, including two-dimensional nmr and hresims data. like the previously isolated pandarosides a-d (13-16), the new compounds 1-12 share an unusual oxidized d-ring and a cis c/d ring junction. the absolute confi ... | 2010 | 20614907 |
| synthesis and activity of azaterphenyl diamidines against trypanosoma brucei rhodesiense and plasmodium falciparum. | a series of azaterphenyl diamidines has been synthesized and evaluated for in vitro antiprotozoal activity against both trypanosoma brucei rhodesiense (t. b. r.) and plasmodium falciparum (p. f.) and in vivo efficacy in the stib900 acute mouse model for t. b. r. six of the 13 compounds showed ic(50) values less than 7 nm against t. b. r. twelve of those exhibited ic(50) values less than 6 nm against p. f. and six of those showed ic(50) values 0.6 nm, which are more than 25-fold as potent as fura ... | 2009 | 19699098 |
| phase ii evaluation of sensitivity and specificity of pcr and nasba followed by oligochromatography for diagnosis of human african trypanosomiasis in clinical samples from d.r. congo and uganda. | the polymerase chain reaction (pcr) and nucleic acid sequence-based amplification (nasba) have been recently modified by coupling to oligochromatography (oc) for easy and fast visualisation of products. in this study we evaluate the sensitivity and specificity of the pcr-oc and nasba-oc for diagnosis of trypanosoma brucei gambiense and trypanosoma brucei rhodesiense human african trypanosomiasis (hat). | 2010 | 20625557 |
| adenosine kinase of t. b. rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2h-pyrazol-3-yl]morpholine using chemical proteomics. | human african trypanosomiasis (hat), a major parasitic disease spread in africa, urgently needs novel targets and new efficacious chemotherapeutic agents. recently, we discovered that 4-[5-(4-phenoxyphenyl)-2h-pyrazol-3-yl]morpholine (compound 1) exhibits specific antitrypanosomal activity with an ic(50) of 1.0 microm on trypanosoma brucei rhodesiense (t. b. rhodesiense), the causative agent of the acute form of hat. | 2009 | 19707572 |
| synthesis and sar of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity. | a series of alkanediamide-linked bisbenzamidines was synthesized and tested in vitro against a drug-sensitive strain of trypanosoma brucei brucei, a drug-resistant strain of trypanosoma brucei rhodesiense and pneumocystiscarinii. bisbenzamidines linked with longer alkanediamide chains were potent inhibitors of both strains of t. brucei. however, bisbenzamidines linked with shorter alkanediamide chains were the most potent compounds against p. carinii. n,n'-bis[4-(aminoiminomethyl)phenyl] hexaned ... | 2009 | 19736009 |
| synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif. | forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. activities of compounds 1-48 against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moi ... | 2009 | 19757840 |