| synthesis, dna binding, fluorescence measurements and antiparasitic activity of dapi related diamidines. | a novel series of extended dapi analogues were prepared by insertion of either a carbon-carbon triple bond (16a-d) or a phenyl group (21a,b and 24) at position-2. the new amidines were evaluated in vitro against both trypanosoma brucei rhodesiense (t. b. r.) and plasmodium falciparum (p. f.). five compounds (16a, 16b, 16d, 21a, 21b) exhibited ic(50) values against t. b. r. of 9nm or less which is two to nine folds more effective than dapi. the same five compounds exhibited ic(50) values against ... | 2010 | 20031421 |
| antitrypanosomal activity of 1,2-dihydroquinolin-6-ols and their ester derivatives. | the current chemotherapy for second stage human african trypanosomiasis is unsatisfactory. a synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (tdr20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. while 6-ether derivatives were less active than the lead compound, several n1-substituted derivatives displayed nanomolar ic(50) values against t. b. rhodesiense stib90 ... | 2010 | 20047276 |
| assessment of anti-protozoal activity of plants traditionally used in ecuador in the treatment of leishmaniasis. | for the assessment of the in vitro anti-protozoal potential of plants traditionally used in ecuador in the treatment of leishmaniasis, a combined approach based on interviews with healers as well as a literature search was carried out. | 2010 | 20064594 |
| antiprotozoal, antimycobacterial and cytotoxic potential of twenty-three british and irish red algae. | as part of our continuing research on seaweeds, we have screened the crude extracts of 23 red marine algae collected from england and ireland. the clinically important blood-stage life forms of trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and mycobacterium tuberculosis were used as test organisms in the in vitro assays. the selectivity of the extracts was determined by using mammalian skeletal myoblast (l6) cells. all algal extracts showed activity against t. brucei rhodesiense, ... | 2010 | 20077438 |
| 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 |
| in vitro activity and preliminary toxicity of various diamidine compounds against trypanosoma evansi. | trypanosoma evansi is an animal pathogenic protozoan, causing a wasting disease called surra, which is broadly distributed in a wide range of mammalian hosts. chemotherapy is the most efficient control method, which depends on four drugs. unfortunately, with the appearance of resistance to these drugs, their effective use is threatened, emphasising a need to find new drugs. diamidines bind to the minor groove of dna at at-rich sites and exert their anti-trypanosomal activity by inhibiting one or ... | 2010 | 20149544 |
| inhibitory activity of marine sponge-derived natural products against parasitic protozoa. | in this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone d (11) and 11 beta-acetoxyspongi-12 ... | 2010 | 20161970 |
| 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 |
| emerging trends in the diagnosis of human african trypanosomiasis. | human african trypanosomiasis (hat) or sleeping sickness is caused by protozoan parasites trypanosoma brucei gambiense and t. b. rhodesiense. despite the enormous technological progress in molecular parasitology in recent years, the diagnosis of hat is still problematic due to the lack of specific tools. to date, there are two realities when it comes to hat; the first one being the world of modern experimental laboratories, equipped with the latest state-of-the-art technology, and the second bei ... | 2010 | 20380768 |
| comparative detection of trypanosomal dna by loop-mediated isothermal amplification and pcr from flinders technology associates cards spotted with patient blood. | we analyzed dna eluted from fta (flinders technology associates) cards spotted with blood from human african trypanosomiasis (hat) patients admitted at lwala hospital in eastern uganda and kaliua health centre in northwestern tanzania. the aims were to evaluate loop-mediated isothermal amplification (lamp) for detection of trypanosomal dna in clinical samples and to characterize the infecting trypanosomes to the subspecies level. lamp targeting the trypanozoon conserved random inserted mobile el ... | 2010 | 20410347 |
| the human trypanolytic factor: a drug shaped naturally. | african trypanosomes are responsible for sleeping sickness in man and nagana in cattle, which are both tremendous health burdens in africa. most african trypanosome species are killed by human serum. this is due to a serum trypanolytic particle specific of some old world monkeys and great apes, an hdl subclass containing two proteins which appeared recently in mammalian evolution, apolipoprotein l1 and haptoglobin related protein. nevertheless, two african trypanosome species, trypanosoma brucei ... | 2010 | 20429865 |
| 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 |
| antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (phaeophyceae) from british and irish waters. | in the continuation of our research on seaweeds, crude extracts of 21 brown algae collected from the south coast of england and the west coast of ireland were screened for in vitro trypanocidal, leishmanicidal and antimycobacterial activities. mammalian stages of a small set of parasitic protozoa; i.e. trypanosoma brucei rhodesiense, t. cruzi and leishmania donovani, and the tubercle bacillus mycobacterium tuberculosis were used as test organisms. the extracts were also evaluated for selectivity ... | 2010 | 20564461 |
| 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 |
| antiprotozoal activity of melampyrum arvense and its metabolites. | an activity guided isolation of the h(2)o subextract of the crude extract of melampyrum arvense l. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8-epi-loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7-o-β-glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9-o-β-glucopyranoside (9); and benzoic acid (10). β-sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the chcl(3) sub ... | 2011 | 20623589 |
| 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 |
| the trypanolytic factor-mechanism, impacts and applications. | the trypanosoma brucei subspecies t. brucei brucei is non-human infective due to susceptibility to lysis by trypanolytic factor (tlf) in human serum. reviewed here are the advances which have revealed apolipoprotein l1 (apol1), found in high density lipoprotein, as the lysis-inducing component of tlf, the means of uptake via haptoglobin-related protein receptor and the mechanism of resistance in t. b. rhodesiense via its serum resistance-associated (sra) protein. the first practical steps to app ... | 2010 | 20646962 |
| association of trypanolytic apol1 variants with kidney disease in african americans. | african americans have higher rates of kidney disease than european americans. here, we show that, in african americans, focal segmental glomerulosclerosis (fsgs) and hypertension-attributed end-stage kidney disease (h-eskd) are associated with two independent sequence variants in the apol1 gene on chromosome 22 {fsgs odds ratio = 10.5 [95% confidence interval (ci) 6.0 to 18.4]; h-eskd odds ratio = 7.3 (95% ci 5.6 to 9.5)}. the two apol1 variants are common in african chromosomes but absent from ... | 2010 | 20647424 |
| genetics. kidney disease is parasite-slaying protein's downside. | | 2010 | 20647431 |
| a spectrum of disease in human african trypanosomiasis: the host and parasite genetics of virulence. | for over 50 years it has been known that there are considerable differences in the severity and rate of progression of both trypanosoma brucei rhodesiense and t. b. gambiense infection between individuals. yet research into the factors, whether parasite or host, which control virulence in human african trypanosomiasis is in its infancy. in this paper we review the clinical evidence for virulence variation and the epidemiological and experimental data that give clues as to the mechanisms involved ... | 2010 | 20663245 |
| trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among trypanosoma brucei subspecies. | trypanosoma brucei rhodesiense and t. b. gambiense are known causes of human african trypanosomiasis (hat), or "sleeping sickness," which is deadly if untreated. we previously reported that a specific inhibitor of trypanosome alternative oxidase (tao), ascofuranone, quickly kills african trypanosomes in vitro and cures mice infected with another subspecies, non-human infective t. b. brucei, in in vivo trials. as an essential factor for trypanosome survival, tao is a promising drug target due to ... | 2010 | 20688188 |
| bromopyrrole alkaloids as lead compounds against protozoan parasites. | in the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide b (3) and dispacamide d (4), stevensine (5) and spongiacidin b (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide b (8) and longamide a (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau'amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin a (13), and agelongine (14), obtained from marine sponges belonging to axinella and agelas ... | 2010 | 20714430 |
| diamidines for human african trypanosomiasis. | aromatic diamidines are potent trypanocides. pentamidine, a diamidine, has been used for more than 60 years to treat human african trypanosomiasis (hat); however, the drug must be administered parenterally and is active against first-stage hat only, prior to the parasites causing neurological deterioration through invasion of the cns. a major research effort to design novel diamidines has led to the development of orally active prodrugs and, remarkably, a new generation of compounds that can pen ... | 2010 | 20721830 |
| antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected tanzanian medicinal plants. | the antiplasmodial, anti-trypanosomal and anti-leishmanial activity of 25 plant extracts obtained from seven tanzanian medicinal plants: annickia (enantia) kummeriae (annonaceae), artemisia annua (asteraceae), pseudospondias microcarpa (anacardiaceae), drypetes natalensis (euphorbiaceae), acridocarpus chloropterus (malpighiaceae), maytenus senegalensis (celastraceae) and neurautanenia mitis (papilonaceae), were evaluated in vitro against plasmodium falciparum k1, trypanosoma brucei rhodesiense s ... | 2009 | 20734703 |
| mechanism of trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor. | human innate immunity against most african trypanosomes, including trypanosoma brucei brucei, is mediated by a minor subclass of toxic serum hdl, called trypanosome lytic factor-1 (tlf-1). this hdl contains two primate specific proteins, apolipoprotein l-1 and haptoglobin (hp)-related protein, as well as apolipoprotein a-1. these assembled proteins provide a powerful defense against trypanosome infection. trypanosoma brucei rhodesiense causes human african sleeping sickness because it has evolve ... | 2010 | 20805508 |
| antiprotozoal activities of some constituents of markhamia tomentosa (bignoniaceae). | phytochemical investigation of an ethyl-acetate extract of the stem bark of markhamia tomentosa (bignoniaceae), which had good antimalarial activity in vitro, resulted in the isolation of eight known compounds: 2-acetylnaphtho[2,3-b]furan-4,9-dione (1), 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-dione (2), oleanolic acid (3), pomolic acid (4), 3-acetylpomolic acid (5), tormentic acid (6), beta-sitosterol (7) and beta-sitosterol-3-o-beta-d-glucopyranoside (8). the structures of these compounds wer ... | 2010 | 20819307 |
| phytochemical investigation of verbesina turbacensis kunth: trypanosome cysteine protease inhibition by (-)-bornyl esters. | the bark and leaf essential oils of verbesina turbacensis were obtained by hydrodistillation and analyzed by gc-ms. the bark oil of the plant was composed mainly of monoterpene hydrocarbons (83.5-90.4%), predominately alpha-pinene, while the leaf oil was composed mainly of sesquiterpene hydrocarbons, dominated by germacrene-d (29.1-36.9%), and delta-elemene (21.7-22.1%). three bornyl hydroxycinnamic esters isolated from the acetone bark extract were found to inhibit the cysteine protease, rhodes ... | 2010 | 20839609 |
| experiences with an in-training community service model in the control of zoonotic sleeping sickness in uganda. | by 2006, the acute and zoonotic tripanosoma brucei rhodesiense sleeping sickness in uganda was spreading northward, leading to fear of a merger with the chronic tripanosoma brucei gambiese type that affects people in the northwest of the country. eliminating infection in cattle was urgent because they had been confirmed to be spreading the zoonotic type, and eliminating infection would reduce the animal reservoir and subsequently reduce transmission of sleeping sickness. in this article, we desc ... | 2010 | 20847337 |
| 2-hexadecynoic acid inhibits plasmodial fas-ii enzymes and arrests erythrocytic and liver stage plasmodium infections. | acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. in this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (hdas) and evaluated their in vitro activity against erythrocytic (blood) stages of plasmodium falciparum and liver stages of plasmodium yoelii infections. since the type ii fatty acid biosynthesis pathway (pffas-ii) has recently been shown to be indispensable for liver stage malaria parasites, t ... | 2010 | 20855214 |
| antiprotozoal activity of drimane and coloratane sesquiterpenes towards trypanosoma brucei rhodesiense and plasmodium falciparum in vitro. | the extracts and 12 sesquiterpenes obtained from the east african medicinal plant warburgia ugandensis sprague (canellaceae) were assessed for their antiplasmodial activity against the chloroquine-sensitive (3d7) and chloroquine-resistant (k1) strains of plasmodium falciparum and antitrypanosomal activity against trypanosoma brucei rhodesiense. the dichloromethane extract displayed strong antiplasmodial and antitrypanosomal activities with ic(50) values of 8.10 and 1.10 µg/ml against k1 strain o ... | 2010 | 20878696 |
| chemotherapy against human african trypanosomiasis: is there a road to success? | for over fifty years, human african trypanosomiasis (hat, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against t. brucei spp. and an acceptable ... | 2010 | 20961469 |
| [the unexpected: chronic renal insufficiency, parasitism, and selective advantage]. | | 2010 | 20964076 |
| the atlas of human african trypanosomiasis: a contribution to global mapping of neglected tropical diseases. | following world health assembly resolutions 50.36 in 1997 and 56.7 in 2003, the world health organization (who) committed itself to supporting human african trypanosomiasis (hat)-endemic countries in their efforts to remove the disease as a public health problem. mapping the distribution of hat in time and space has a pivotal role to play if this objective is to be met. for this reason who launched the hat atlas initiative, jointly implemented with the food and agriculture organization of the un ... | 2010 | 21040555 |
| optimization of purine-nitrile tbcatb inhibitors for use in vivo and evaluation of efficacy in murine models. | there are currently only four clinical drugs available for treating human african trypanosomiasis (hat), three of which were developed over 60 years ago. despite years of effort, there has been relatively little progress towards identifying orally available chemotypes active against the parasite in vivo. here, we report the lead optimization of a purine-nitrile scaffold that inhibits the essential tbcatb protease and its evaluation in murine models. a lead inhibitor that had potent activity agai ... | 2010 | 21051236 |
| lamp for human african trypanosomiasis: a comparative study of detection formats. | loop-mediated isothermal amplification (lamp) is at the forefront of the search for innovative diagnostics for human african trypanosomiasis (hat). several simple endpoint detection methods have been developed for lamp and here we compare four of these: (i) visualization of turbidity; (ii) addition of hydroxynaphthol blue before incubation; (iii) addition of calcein with mncl₂ before incubation and (iv) addition of quant-it picogreen after incubation. these four methods were applied to four lamp ... | 2010 | 21072228 |
| a global sensitivity analysis for african sleeping sickness. | african sleeping sickness is a parasitic disease transmitted through the bites of tsetse flies of the genus glossina. we constructed mechanistic models for the basic reproduction number, r0, of trypanosoma brucei gambiense and trypanosoma brucei rhodesiense, respectively the causative agents of west and east african human sleeping sickness. we present global sensitivity analyses of these models that rank the importance of the biological parameters that may explain variation in r0, using paramete ... | 2010 | 21078220 |
| synthesis and antitrypanosomal evaluation of derivatives of n-benzyl-1,2-dihydroquinolin-6-ols: effect of core substitutions and salt formation. | analogs of the trypanocidal lead compound 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were prepared to extend the structure-activity relationship in this series of molecules, improve the in vivo antitrypanosomal activity of the lead, and determine whether ester prodrugs are needed to overcome the instability of the dihydroquinolin-6-ols. two of the most active compounds identified in this study were 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxy)be ... | 2010 | 21112788 |
| focus-specific clinical profiles in human african trypanosomiasis caused by trypanosoma brucei rhodesiense. | diverse clinical features have been reported in human african trypanosomiasis (hat) foci caused by trypanosoma brucei rhodesiense (t.b.rhodesiense) giving rise to the hypothesis that hat manifests as a chronic disease in south-east african countries and increased in virulence towards the north. such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. our molecular tools allow us to study t ... | 2010 | 21151878 |
| complete structural assignment of serratol, a cembrane-type diterpene from boswellia serrata, and evaluation of its antiprotozoal activity. | from the dichloromethane extract obtained from the gum resin of boswellia serrata roxb. (burseraceae), a well-known medicinal plant resin ("indian olibanum"), the cembrane-type diterpene serratol was isolated in high yield. its structure, previously reported without clear specification of double-bond geometry and without specification of stereochemistry, was reanalysed by means of spectroscopic measurements and unambiguously assigned as s(-)-cembra-3 e,7 e,11 e-triene-1-ol. full assignment of al ... | 2010 | 21157686 |
| improved inhibitors of trypanothione reductase by combination of motifs: synthesis, inhibitory potency, binding mode, and antiprotozoal activities. | trypanothione reductase (tr) is an essential enzyme in the trypanothione-based redox metabolism of trypanosomatid parasites. this system is absent in humans and, therefore, offers a promising target for the development of selective new drugs against african sleeping sickness and chagas' disease. over the past two decades, a variety of nonpeptidic small-molecule ligands of the parasitic enzyme were discovered. a current goal is to decipher the binding mode of these known inhibitors in order to op ... | 2010 | 21165935 |
| synthesis and antiprotozoal activity of n-alkoxy analogues of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine with improved human blood-brain barrier permeability. | to improve the blood-brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five n-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and n-alkoxy-n-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). this involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. the blood-brain ... | 2010 | 21175162 |
| dicationic phenyl-2,2'-bichalcophenes and analogues as antiprotozoal agents. | a series of phenyl-2,2'-bichalcophene diamidines 1a-h were synthesized from the corresponding dinitriles either via a direct reaction with lin(tms)₂, followed by deprotection with ethanolic hcl or through the bis-o-acetoxyamidoxime followed by hydrogenation in acetic acid and etoh over pd-c. these diamidines show a wide range of dna affinities as judged from their δt(m) values which are remarkably sensitive to replacement of a furan unit with a thiophene one. these differences are explained in t ... | 2010 | 21194955 |
| apol1 variants and kidney disease. there is no such thing as a free lunch. | a recent study by genovese et al. unraveled the findings of the intensively discussed gene region around myh9 and its association with non-diabetic chronic kidney disease in african-americans. first, it is not the genetic variation in myh9 but in the neighbouring apol1 that causes the strong association with disease in african-americans and second, the study showed strong evidence for a positive selection against vulnerability for trypanosoma brucei rhodesiense infection but at the price of a hi ... | 2011 | 21216884 |
| dental management of the tropical disease human african trypanosomiasis: an unusual case of pseudobulbar palsy. | human african trypanosomiasis (sleeping sickness) is a parasitic tropical disease endemic to sub-saharan africa. due to migration and holiday travel patterns cases are increasing in the united kingdom. the neurological sequelae have dental management implications both directly from the consequent physical disability and indirectly from the oral side-effects of the medications used to manage symptoms. changes in disease demographics require the dental profession to increase its awareness of migra ... | 2011 | 21217721 |
| improved inhibitors of trypanothione reductase by combination of motifs: synthesis, inhibitory potency, binding mode, and antiprotozoal activities. | trypanothione reductase (tr) is an essential enzyme in the trypanothione-based redox metabolism of trypanosomatid parasites. this system is absent in humans and, therefore, offers a promising target for the development of selective new drugs against african sleeping sickness and chagas' disease. over the past two decades, a variety of nonpeptidic small-molecule ligands of the parasitic enzyme were discovered. a current goal is to decipher the binding mode of these known inhibitors in order to op ... | 2010 | 21275053 |
| factors associated with acquisition of human infective and animal infective trypanosome infections in domestic livestock in western kenya. | trypanosomiasis is regarded as a constraint on livestock production in western kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. to assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (pcr), in a range of domestic livestock at the local scale in busia, ke ... | 2011 | 21311575 |
| phylogeography and taxonomy of trypanosoma brucei. | characterizing the evolutionary relationships and population structure of parasites can provide important insights into the epidemiology of human disease. | 2011 | 21347445 |
| identification and characterization of cysteine proteinases of trypanosoma evansi. | trypanosoma evansi is a causative agent of 'surra', a common haemoprotozoan disease of livestock in india causing high morbidity and mortality in disease endemic areas. the proteinases released by live and dead trypanosomes entail immunosuppression in the infected host, which immensely contribute in disease pathogenesis. cysteine proteinases are identified in the infectious cycle of trypanosomes such as cruzain from trypanosoma cruzi, rhodesain or brucipain from trypanosoma brucei rhodesiense an ... | 2011 | 21350794 |
| clinical presentation of t.b. rhodesiense sleeping sickness in second stage patients from tanzania and uganda. | a wide spectrum of disease severity has been described for human african trypanosomiasis (hat) due to trypanosoma brucei rhodesiense (t.b. rhodesiense), ranging from chronic disease patterns in southern countries of east africa to an increase in virulence towards the north. however, only limited data on the clinical presentation of t.b. rhodesiense hat is available. from 2006-2009 we conducted the first clinical trial program (impamel iii) in t.b. rhodesiense endemic areas of tanzania and uganda ... | 2011 | 21407802 |
| in vitro screening of traditional south african malaria remedies against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. | three hundred extracts were prepared from plants traditionally used in south africa to treat malaria and screened in vitro for activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/ml, the ic (50) values against all four protozoal parasites and cytotoxic ic (50)s against rat myoblast l6 cells were determined. amongst the most notable re ... | 2011 | 21412695 |
| antiplasmodial and antitrypanosomal activity of tanshinone-type diterpenoids from salvia miltiorrhiza. | in a medium throughput screen of 880 plant and fungal extracts for antiprotozoal activity, a dichloromethane extract of salvia miltiorrhiza roots was active against both trypanosoma brucei rhodesiense and plasmodium falciparum. with hplc-based activity profiling in combination with on- and off-line spectroscopic methods (pda, -ms (n), hr-ms, microprobe nmr), the active compounds were identified as tanshinone-type diterpenoids. subsequent isolation and structure elucidation yielded the known subs ... | 2011 | 21412700 |
| influence of trypanocidal therapy on the haematology of vervet monkeys experimentally infected with trypanosoma brucei rhodesiense. | the aim of this study was to characterise the sequential haematological changes in vervet monkeys infected with trypanosoma brucei rhodesiense and subsequently treated with sub-curative diminazene aceturate (da) and curative melarsoprol (melb) trypanocidal drugs. fourteen vervet monkeys, on a serial timed-kill pathogenesis study, were infected intravenously with 10(4) trypanosomes of a stabilate t. b. rhodesiense ketri 2537. they were treated with da at 28 days post infection (dpi) and with melb ... | 2011 | 21420376 |
| exploration of larger central ring linkers in furamidine analogues: synthesis and evaluation of their dna binding, antiparasitic and fluorescence properties. | the effects of replacing the central furan ring of furamidine with indole and benzimidazole on their dna binding affinity, antiparasitic activity and fluorescence are reported. the bis-cyanophenylindoles required to make the corresponding amidines were prepared by sequential stille and/or suzuki coupling reactions. the bis-cyanophenylbenzimidazoles were obtained by coupling 4-cyanobenzaldehydes with the appropriate cyano substituted phenylenediamine. the bis-nitriles were converted to the diamid ... | 2011 | 21421317 |
| antiparasitic compounds from cupania cinerea with activities against plasmodium falciparum and trypanosoma brucei rhodesiense. | in a survey of plants from ecuador with antiprotozoal activity, cupania cinerea was found to show significant in vitro activity against the plasmodium falciparum k1 strain and trypanosoma brucei rhodesiense. subsequently, activity-guided isolation of the n-hexane and dichloromethane extracts from the bark of c. cinerea afforded two diterpene glycosides (1 and 2), named cupacinoside and 6'-de-o-acetylcupacinoside, and a lactonized triterpene bearing an oxepin moiety named cupacinoxepin (3), toget ... | 2011 | 21438586 |
| new antitrypanosomal tetranotriterpenoids from azadirachta indica. | organic extracts of the leaves of azadirachta indica a. juss. yielded ten antitrypanosomal terpenoids. three of these (1-3), are novel and are derivatives of nimbolide and nimbin. they were extracted from chloroform fraction of methanol extract. these compounds were found to exhibit strong antitrypanosomal activities against trypanosoma brucei rhodesiense with mic values ranging of 6.9, 15.6 and 7.8 µg/ml respectively and were more active than cymerlarsan (a standard drug), which had an mic valu ... | 2010 | 21461147 |
| evaluation of turkish seaweeds for antiprotozoal, antimycobacterial and cytotoxic activities. | as part of our continuing research on seaweeds, crude meoh extracts of two green, three brown and six red algae collected from marmara, black, aegean and mediterranean seas were screened. four parasitic protozoa, i.e. plasmodium falciparum, trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and the tubercle bacillus mycobacterium tuberculosis were used as test organisms for the in vitro assays. the selective toxicity of the extracts was also determined against mammalian l6 cells. all ... | 2011 | 21520472 |
| antiprotozoal activities of traditional medicinal plants from the garhwal region of north west himalaya, india. | in a search for new plant-derived biologically active compounds against protozoan parasites, an ethnopharmacological study was carried out to evaluate extracts from selected 17 traditional medicinal plants which were used by healers from the garhwal region of north west himalaya for the treatment of protozoal infections and fever including malaria. | 2011 | 21527328 |
| antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from ireland. | cyanobacteria (= blue-green algae) are prolific producers of structurally distinct and biologically active metabolites. in the continuation of our search for new sources of anti-infective natural products, we have assessed the in vitro antiprotozoal (plasmodium falciparum, trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani) and antitubercular (mycobacterium tuberculosis) potential of samples of two terrestrial cyanobacteria, nostoc commune (collected when desiccated and wet) and rivul ... | 2011 | 21615033 |
| antitrypanosomal sesquiterpene lactones from saussurea costus. | in the course of a larger screen of 1800 plant and fungal extracts, the ethyl acetate extract of saussurea costus roots potently inhibited the growth of trypanosoma brucei rhodesiense. subsequent hplc based activity profiling led to the identification of the sesquiterpene lactones arbusculin b (1), α-cyclocostunolide (2), costunolide (3), and dehydrocostuslactone (4). they were tested for in vitro antitrypanosomal activities and cytotoxicity alongside the structurally related sesquiterpene lacto ... | 2011 | 21624443 |
| crystal structures of t. b. rhodesiense adenosine kinase complexed with inhibitor and activator: implications for catalysis and hyperactivation. | the essential purine salvage pathway of trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of human african trypanosomiasis. unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. one of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (amp) utilizing adenosine triphosphate (atp) as the preferred phosphoryl donor. | 2011 | 21629723 |
| antitrypanosomal activity of some medicinal plants from nigerian ethnomedicine. | human african trypanosomiasis is a neglected tropical disease with complex clinical presentation, diagnosis, and difficult treatment. the available drugs for the treatment of trypanosomiasis are old, expensive, and less effective, associated with severe adverse reactions and face the problem of drug resistance. this situation underlines the urgent need for the development of new, effective, cheap, and safe drugs for the treatment of trypanosomiasis. the search for new antitrypanosomal agents in ... | 2011 | 21789586 |
| antiplasmodial and antitrypanosomal activity of pyrethrins and pyrethroids. | in a screen of 1800 plant and fungal extracts for antiplasmodial, antitrypanosomal, and leishmanicidal activity, the n-hexane extract of chrysanthemum cinerariifolium (trevir.) vis. flowers showed strong activity against plasmodium falciparum. we isolated the five pyrethrins [i.e., pyrethrin ii (1), jasmolin ii (2), cinerin ii (3), pyrethrin i (4), and jasmolin i (5)] from this extract. these were tested together with 15 synthetic pyrethroids for their activity against p. falciparum and trypanos ... | 2011 | 21786822 |
| encecalol angelate, an unstable chromene from ageratum conyzoides l.: total synthesis and investigation of its antiprotozoal activity. | in agreement with ethnomedicinal reports, the dichloromethane extract of ageratum conyzoides l. (asteraceae) was recently shown to be of considerable activity against trypanosoma brucei rhodesiense, the etiologic agent of east african human trypanosomiasis (east african sleeping sickness). isolated compounds, namely, methoxylated flavonoids as well as the chromene derivative encecalol methyl ether, were less active than the crude extract. the activity of the extract was found to decrease conside ... | 2011 | 21708240 |
| mass-treatment and insecticide-spraying of animal reservoirs for emergency control of rhodesiense sleeping sickness in uganda. | | 2011 | 21715734 |
| endosomal localization of the serum resistance-associated protein in african trypanosomes confers human infectivity. | trypanosoma brucei rhodesiense is the causative agent of human african sleeping sickness. while the closely related subspecies t. brucei brucei is highly susceptible to lysis by a subclass of human high-density lipoproteins (hdl) called trypanosome lytic factor (tlf), t. brucei rhodesiense is resistant and therefore able to establish acute and fatal infections in humans. this resistance is due to expression of the serum resistance-associated (sra) gene, a member of the variant surface glycoprote ... | 2011 | 21705681 |
| evaluation of an ethnopharmacologically selected bhutanese medicinal plants for their major classes of phytochemicals and biological activities. | as many as 229 medicinal plants have been currently used in the bhutanese traditional medicine (btm) as a chief ingredient of polyherbal formulations and these plants have been individually indicated for treating various types of infections including malaria, tumor, and microbial. we have focused our study only on seven species of these plants. | 2011 | 21741462 |
| human african trypanosomiasis: a review of non-endemic cases in the past 20 years. | human african trypanosomiasis (hat) is caused by sub-species of the parasitic protozoan trypanosoma brucei and is transmitted by tsetse flies, both of which are endemic only to sub-saharan africa. several cases have been reported in non-endemic areas, such as north america and europe, due to travelers, ex-patriots or military personnel returning from abroad or due to immigrants from endemic areas. in this paper, non-endemic cases reported over the past 20 years are reviewed; a total of 68 cases ... | 2011 | 21683638 |
| using detergent to enhance detection sensitivity of african trypanosomes in human csf and blood by loop-mediated isothermal amplification (lamp). | the loop-mediated isothermal amplification (lamp) assay, with its advantages of simplicity, rapidity and cost effectiveness, has evolved as one of the most sensitive and specific methods for the detection of a broad range of pathogenic microorganisms including african trypanosomes. while many lamp-based assays are sufficiently sensitive to detect dna well below the amount present in a single parasite, the detection limit of the assay is restricted by the number of parasites present in the volume ... | 2011 | 21829738 |
| an optimized in vitro blood-brain barrier model reveals bidirectional transmigration of african trypanosome strains. | the transmigration of african trypanosomes across the human blood-brain barrier (bbb) is the critical step during the course of the human african trypanosomiasis (hat). the parasites trypanosoma brucei gambiense and t. b. rhodesiense are transmitted to humans during a bite of tsetse flies. trypanosomes multiply within the blood stream and finally invade the central nervous system (cns), which leads to the death of untreated patients. in order to establish an adequate in vitro bbb model for paras ... | 2011 | 21737496 |
| prevalence of trypanosoma sp. in cattle from tanzania estimated by conventional pcr and loop-mediated isothermal amplification (lamp). | this study compared the prevalence of trypanosome infections estimated by pfr-loop-mediated isothermal amplification (lamp) with conventional polymerase chain reaction (pcr) tests. one hundred forty eight cattle blood samples were collected from robanda village, mara region, tanzania in april 2008. in conventional pcr, four sets of primers, specific for the detection of trypanosoma sp., trypanosoma brucei rhodesiense, trypanosoma vivax, and trypanozoon, as well as a modified lamp were used. conv ... | 2011 | 21739311 |
| triterpenoids with rare carbon skeletons from salvia hydrangea: antiprotozoal activity and absolute configurations. | salvadione c (1) and perovskone b (2), two new triterpenoids with rare carbon skeletons, were isolated from an antiplasmodial n-hexane extract of salvia hydrangea. the absolute configuration was determined by comparison of experimental and calculated electronic circular dichroism (ecd) spectra. in vitro activity against plasmodium falciparum k1 strain, trypanosoma brucei rhodesiense stib 900 strain, and cytotoxicity in rat myoblast (l6) cells were determined. compounds 1 and 2 showed in vitro an ... | 2011 | 21967089 |
| 9ß-Hydroxyparthenolide Esters from Inula montbretiana and Their Antiprotozoal Activity. | In continuation of ongoing studies on the potential of natural products as antiprotozoal leads or drugs, it was found that the CH (2)Cl (2) extract obtained from the flowering aerial parts of INULA MONTBRETIANA DC. (Asteraceae, tribe Inuleae) displays antiprotozoal activity, especially against TRYPANOSOMA BRUCEI RHODESIENSE (IC (50): 3.38?µg/mL). Isolation of the possible active constituents led to the identification of six sesquiterpene lactones, all esters of 9 ß-hydroxyparthenolide. Two iso ... | 2011 | 22109834 |
| Biological evaluation of glycosyl-isoindigo derivatives against the pathogenic agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis). | The biological activities of diversely substituted glycosyl-isoindigo derivatives against the causative agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis) are reported. Some of the compounds tested showed interesting activities with good selectivity indices, particularly against Trypanosoma brucei rhodesiense. These results suggested, for the first time, that glycosyl-isoindigo derivatives could be of interest for the discovery of new lead comp ... | 2011 | 21937228 |
| Bis(oxyphenylene)benzimidazoles: A novel class of anti-Plasmodium falciparum agents. | A small library of 26 2,2'-[alkane-a,?-diylbis(oxyphenylene)]bis-1H-benzimidazoles has been prepared and evaluated against Giardia intestinalis, Entamoeba histolytica, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. Among the tested compounds, eight derivatives (17, 19, 20, 24, 27, 30, 32 and 35) exhibited an anti-Plasmodium falciparum activity characterized by IC(50) values in the range of 180-410nM (0.11-0.21µg/mL) and selectivity indexes (IC( ... | 2011 | 22061825 |
| Molecular modeling study and synthesis of novel dicationic flexible triaryl guanidines and imidamides as antiprotozoal agents. | A new series of fourteen dicationic flexible triaryl bis-guanidines 3a,b, bis-N-substituted guanidines 7a,b and 8a,b as well as bis-imidamides 9-12a,b having a 1,3- or 1,4-diphenoxybenzene scaffold backbone were synthesized. The in vitro activity of the novel dications as antiprotozoal agents against Trypanosoma brucei rhodesiense (T.b.r.) and Plasmodium falciparum (P.f.) was assessed. Interestingly, six of the newly synthesized dications viz 3a,b, 7a,b and 8a,b were more active against P.f. tha ... | 2011 | 22005186 |
| synthesis and in vitro antiprotozoal activities of 5-phenyliminobenzo[a]phenoxazine derivatives. | a series of 5-phenyliminobenzo[a]phenoxazine derivatives were synthesized. the in vitro antiprotozoal activities were evaluated against plasmodium falciparum k1, trypanosoma cruzi, leishmania donovani and trypanosoma brucei rhodesiense. n,n-diethyl-5-((4-methoxyphenyl)imino)-5h-benzo[a]phenoxazin-9-amine shows ic(50)=0.040 μmol l(-1) with a selective index of 1425 against plasmodium falciparum k1. | 2011 | 21868222 |
| lipid metabolism and other metabolic changes in vervet monkeys experimentally infected with trypanosoma brucei rhodesiense. | background human african trypanosomiasis is associated with metabolic changes which have not been well characterized. methods chlorocebus aethiops were experimentally infected with trypanosoma brucei rhodesiense and late-stage disease induced at 28 days post-infection. ear prick blood for glucose determination and blood samples were obtained at weekly intervals for 56 days. analysis was carried out using dry chemistry analysis. results in early infection, there was a significant increase in c ... | 2011 | 22070162 |
| new n-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds. | the 4-methylpiperazinyl group was inserted as substituent at the bridgehead of bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side chains. the new compounds were tested in vitro for their activities against the multidrug-resistant k(1) strain of plasmodium falciparum and trypanosoma brucei rhodesiense (stib 900). the results were compared to those of formerly prepared analogues and of drugs in use. a couple of bicyclo-octyl ω-(4-piperazin-1-yl)alkanoates showed high an ... | 2011 | 22136906 |
| complete coding sequence, sequence analysis and transmembrane topology modelling of trypanosoma brucei rhodesiense putative oligosaccharyl transferase (tbost ii). | the partial nucleotide sequence of putative trypanosoma brucei rhodesiense oligosaccharyl transferase gene was previously reported. here, we describe the determination of its full-length nucleotide sequence by inverse pcr (ipcr), subsequent biological sequence analysis and transmembrane topology modelling. the full-length dna sequence has an open reading frame (orf) of 2406 bp and encodes a polypeptide of 801 amino acid residues. protein and dna sequence analyses revealed that homologues within ... | 2011 | 22145535 |
| in vitro antiprotozoal activity of extracts of five turkish lamiaceae species. | the in vitro antiprotozoal activities of crude methanolic extracts from the aerial parts of five lamiaceae plants (salvia tomentosa, s. sclarea, s. dichroantha, nepeta nuda subsp. nuda and marrubium astracanicum subsp. macrodon) were evaluated against four parasitic protozoa, i.e. trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and plasmodium falciparum. the cytotoxic potentials of the extracts on l6 cells were also evaluated. melarsoprol, benznidazole, miltefosine, chloroquine and ... | 2011 | 22224291 |
| screening and hplc-based activity profiling for new antiprotozoal leads from european plants. | based on a survey of remedies used in renaissance europe to treat malaria, we prepared and screened a library of 254 extracts from 61 plants for antiplasmodial activity in vitro. hplc-based activity profiling was performed for targeted identification of active constituents in extracts. one of the most remarkable results was the identification of onopordopicrin, a germacranolide sesquiterpene lactone isolated from arctium nemorosum as a potent inhibitor of p. falciparum with an ic(50) of 6.9 μm. ... | 2011 | 22396915 |
| role of expression site switching in the development of resistance to human trypanosome lytic factor-1 in trypanosoma brucei brucei. | human high-density lipoproteins (hdls) play an important role in human innate immunity to infection by african trypanosomes with a minor subclass, trypanosome lytic factor-1 (tlf-1), displaying highly selective cytotoxicity to the veterinary pathogen trypanosoma brucei brucei but not against the human sleeping sickness pathogens trypanosoma brucei gambiense or trypanosoma brucei rhodesiense. t. b. rhodesiense has evolved the serum resistance associated protein (sra) that binds and confers resist ... | 2011 | 22226682 |
| assessment of antimicrobial and antiprotozoal activity of the olive oil macerate samples of hypericum perforatum and their lc-dad-ms analyses. | twenty-one samples of traditionally-prepared (home-made) and ready-made (commercial) st. john's wort olive oil macerates were profiled for their in vitro antimicrobial and antiprotozoal activity. their cytotoxic potential was evaluated on mrc-5 fibroblasts. in the antiprotozoal assays, ten of the oils inhibited trypanosoma brucei rhodesiense (ic(50) 15.9-64.5 μg/ml), while only one oil exerted antimicrobial activity towards staphylococcus aureus (ic(50)=88.7 μg/ml). lc-dad-ms data revealed the p ... | 2012 | 23411190 |
| towards an early warning system for rhodesian sleeping sickness in savannah areas: man-like traps for tsetse flies. | in the savannahs of east and southern africa, tsetse flies (glossina spp.) transmit trypanosoma brucei rhodesiense which causes rhodesian sleeping sickness, the zoonotic form of human african trypanosomiasis. the flies feed mainly on wild and domestic animals and are usually repelled by humans. however, this innate aversion to humans can be undermined by environmental stresses on tsetse populations, so increasing disease risk. to monitor changes in risk, we need traps designed specifically to qu ... | 2012 | 23301107 |
| extracellular vesicles from trypanosoma brucei mediate virulence factor transfer and cause host anemia. | intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion, and disease pathology. bloodstream african trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (evs). trypanosome evs contain several flagellar proteins that contribute to virulence, and trypanosoma brucei rhodesiense evs contain the serum resistance-associated protein (sra) necessary for ... | 2016 | 26771494 |
| using molecular data for epidemiological inference: assessing the prevalence of trypanosoma brucei rhodesiense in tsetse in serengeti, tanzania. | measuring the prevalence of transmissible trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of i ... | 2012 | 22303496 |
| an overview of trypanosoma brucei infections: an intense host-parasite interaction. | trypanosoma brucei rhodesiense and t. brucei gambiense, the causative agents of human african trypanosomiasis, are transmitted by tsetse flies. within the vector, the parasite undergoes through transformations that prepares it to infect the human host. sequentially these developmental stages are the replicative procyclic (in which the parasite surface is covered by procyclins) and trypo-epimastigote forms, as well as the non-replicative, infective, metacyclic form that develops in the vector sal ... | 2016 | 28082973 |
| synthesis and antiparasitic activity of new bis-arylimidamides: db766 analogs modified in the terminal groups. | fifteen novel bis-arylimidamide derivatives with various 6-membered (7a-c) and 5-membered (7d-o) heterocyclic rings replacing the terminal pyridyl rings of the lead compound db766{(2,5-bis[2-i-propoxy-4-(2-pyridylimino)aminophenylfuran]}, were prepared and evaluated versus trypanosoma cruzi, leishmania amazonensis, trypanosoma brucei rhodesiense and plasmodium falciparum. compound 7a with pyrimidine replacing the pyridine rings showed good activity versus t. cruzi, t. brucei rhodesiense and p. f ... | 2014 | 24956553 |
| synthesis and antitrypanosomal activities of novel pyridylchalcones. | a library of novel pyridylchalcones were synthesised and screened against trypanosoma brucei rhodesiense. eight were shown to have good activity with the most potent 8 having an ic50 value of 0.29 μm. cytotoxicity testing with human kb cells showed a good selectivity profile for this compound with a selectivity index of 47. little activity was seen when the library was tested against leishmania donovani. in conclusion, pyridylchalcones are promising leads in the development of novel compounds fo ... | 2017 | 28189085 |
| antiprotozoal glutathione derivatives with flagellar membrane binding activity against t. brucei rhodesiense. | a new series of n-substituted s-(2,4-dinitrophenyl)glutathione dibutyl diesters were synthesized to improve in vitro anti-protozoal activity against the pathogenic parasites trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the results obtained indicate that n-substituents enhance the inhibitory properties of glutathione diesters whilst showing reduced toxicity against kb cells as in the cases of compounds 5, 9, 10, 16, 18 and 19. we suggest that the interaction of n-sub ... | 2017 | 28131508 |
| antiprotozoal activity-based profiling of a dichloromethane extract from anthemis nobilis flowers. | a dichlomethane extract of anthemis nobilis flower cones showed promising in vitro antiprotozoal activity against trypanosoma brucei rhodesiense and leishmania donovani, with ic50 values of 1.43 ± 0.50 and 1.40 ± 0.07 μg/ml, respectively. a comprehensive profiling of the most active fractions afforded 19 sesquiterpene lactones, including 15 germacranolides, two seco-sesquiterpenes, one guaianolide sesquiterpene lactone, and one cadinane acid. of these, 13 compounds were found to be new natural p ... | 2017 | 28116906 |
| ent-pimarane and ent-kaurane diterpenes from aldama discolor (asteraceae) and their antiprotozoal activity. | aldama discolor (syn.viguiera discolor) is an endemic asteraceae from the brazilian "cerrado", which has not previously been investigated for its chemical constituents and biological activity. diterpenes are common secondary metabolites found in aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. in this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2 ... | 2016 | 27649126 |
| 3-nitrotriazole-based piperazides as potent antitrypanosomal agents. | novel linear 3-nitro-1h-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. in addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. most 3-nitrotriazole-based derivatives were potent and selective against trypanosoma cruzi parasites, but only one displayed these desired properties against trypanosoma brucei rhodesiense. moreover, two 3-nitrotriazole-based chlorophenylpiperazides were mod ... | 2015 | 26363868 |
| discovery of potent nitrotriazole-based antitrypanosomal agents: in vitro and in vivo evaluation. | 3-nitro-1h-1,2,4-triazole- and 2-nitro-1h-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. all 3-nitrotriazole-based derivatives were extremely potent anti-trypanosoma cruzi agents at sub nm concentrations and exhibited a high degree of selectivity for the parasite. the 2-nitroimidazole analogs were only moderately active against t. cruzi amastigotes and exhibited low selectivity. both types of compound were active against leishmania d ... | 2015 | 26344593 |
| search for antiprotozoal activity in herbal medicinal preparations; new natural leads against neglected tropical diseases. | sleeping sickness, chagas disease, leishmaniasis, and malaria are infectious diseases caused by unicellular eukaryotic parasites ("protozoans"). the three first mentioned are classified as neglected tropical diseases (ntds) by the world health organization and together threaten more than one billion lives worldwide. due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. in vie ... | 2015 | 26248069 |