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antiparasitic activity of c-geranyl flavonoids from mimulus bigelovii.bioactivity-directed fractionation of the meoh fraction of the extract of mimulus bigelovii by means of an axenic leishmania amastigote assay and chromatographic techniques resulted in the isolation of four c-geranyl flavanones, diplacone (1), 3'-o-methyldiplacone (2), 4'-o-methyldiplacone (3), 3'-o-methyldiplacol (4), together with a geranylated flavone, cannflavin a (5). these compounds were separated from m. bigelovii for the first time. all compounds showed moderate antileishmanial activity ...201121796699
stage-specific requirement for isa1 and isa2 proteins in the mitochondrion of trypanosoma brucei and heterologous rescue by human and blastocystis orthologues.isca/isa proteins function as alternative scaffolds for the assembly of fe-s clusters and/or provide iron for their assembly in prokaryotes and eukaryotes. isa are usually non-essential and in most organisms are confined to the mitochondrion. we have studied the function of tbisa1 and tbisa2 in trypanosoma brucei, where the requirement for both of them to sustain cell growth depends on the life cycle stage. the tbisa proteins are abundant in the procyclic form, which contains an active organelle ...201121790804
novel o-glycosidic gossypol isomers and their bioactivities.novel glycosidic gossypol analogs, 7,7'-gossypol diglucoside tetraacetate gs1, 6,7'-gossypol diglucoside tetraacetate gs2, 7,7'-gossypol diglycoside gs1', 6,7'-gossypol diglycoside gs2' were obtained by the ultrasound-assisted reaction of the potassium salt of gossypol with 2,3,4,6-tetra-o-acetyl-a-d-glucopyranosyl bromide under ptc conditions and were fully characterized by 1d nmr ((1)h nmr, (13)c nmr, dept, 1d noe), 2d nmr (hmbc, hmqc), ftir, hrms and hplc. the anticancer activities, cytotoxic ...201121788013
in vitro antitrypanosomal and antileishmanial activity of plants used in benin in traditional medicine and bio-guided fractionation of the most active extract.ethnopharmacological relevance: the aim of the study was to evaluate the in vitro antitrypanosomal and antileishmanial activity of crude extracts of 10 plant species traditionally used in benin to treat parasitic infections. materials and methods: for each species, dichloromethane, methanol and aqueous extracts were tested. their antitrypanosomal and antileishmanial activities were evaluated in vitro on trypanosoma brucei brucei (strain 427) (tbb) and on promastigotes of leishmania mexicana mexi ...201121782916
the effects of combination of methanolic leaf extract of azadirachta indica and diminazene diaceturate in the treatment of experimental trypanosoma brucei brucei infection in rats.to investigate the effects of combination therapy of methanolic leaf extract of azadirachta indica (a. indica) and diminazene diaceturate (dda) in the treatment of experimental trypanosoma brucei brucei (t. brucei brucei) infection in rats.201121771672
the characterization of a unique trypanosoma brucei ß-hydroxybutyrate dehydrogenase.a putative ß-hydroxybutyrate dehydrogenase (ßhbdh) ortholog was identified in trypanosoma brucei, the unicellular eukaryotic parasite responsible for causing african sleeping sickness. the trypanosome enzyme has greater sequence similarity to bacterial sources of soluble ßhbdh than to membrane-bound type i ßhbdh found in higher eukaryotes. the ßhbdh gene was cloned from t. brucei genomic dna and active, recombinant his-tagged enzyme (his(10)-tbßhbdh) was purified to approximate homogeneity from ...201121767577
rna interference in protozoan parasites: achievements and challenges.protozoan parasites that profoundly affect mankind represent an exceptionally diverse group of organisms, including plasmodium, toxoplasma, entamoeba, giardia, trypanosomes and leishmania. despite the overwhelming impact of these parasites, there remain many aspects to be discovered about mechanisms of pathogenesis and how these organisms survive in the host. combined with the ever increasing availability of sequenced genomes, rna interference (rnai), discovered a mere 13 years ago, has enormous ...201121764910
specializations in a successful parasite: what makes the bloodstream-form african trypanosome so deadly?most trypanosomatid parasites have both arthropod and mammalian or plant hosts, and the ability to survive and complete a developmental program in each of these very different environments is essential for life cycle progression and hence being a successful pathogen. for african trypanosomes, where the mammalian stage is exclusively extracellular, this presents specific challenges and requires evasion of both the acquired and innate immune systems, together with adaptation to a specific nutritio ...201121763356
synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold.a short practical synthesis of a new natural product based scaffold (6), based on antitrypanosomal and antimalarial compounds isolated from different plakortis species is described. the scaffold contains a peroxide unit that is surprisingly stable to chemical manipulation elsewhere in the molecule, enabling it to be elaborated into a small library of derivatives. it is stable to ozonolysis, reductive work-up with dimethylsulfide and the wittig reaction with stabilized phosphorus ylides. the scaf ...201121757346
mono-, di- and trisubstituted derivatives of eflornithine: synthesis for in vivo delivery of dl-alpha-difluoromethylornithine in plasma.the aim of this study was to synthesize a series of mono-, di- and trisubstituted derivatives of the human african trypanosomiasis drug eflornithine (alpha-difluoromethylornithine, dmfo, cas 70052-12-9) to determine their partition coefficients, and to assess whether they deliver the parent drug in the plasma. if increased plasma concentrations of eflornithine could be achieved in this way, an oral dosage form would be possible. the derivatives, nine in total, were successfully synthesized by mu ...201121755816
screening a fragment cocktail library using ultrafiltration.ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar k (d), the typical range of fragment-based drug discovery. this method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 da, were screened against medical structural genomics target proteins. the validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the t ...201121750879
poly(a)-specific ribonuclease (parn-1) function in stage-specific mrna turnover in trypanosoma brucei.deadenylation is often the rate-limiting event in regulating the turnover of cellular mrnas in eukaryotes. removal of the poly(a) tail initiates mrna degradation by one of several decay pathways, including deadenylation-dependent decapping followed by 5' to 3' exonuclease decay or 3' to 5' exosome-mediated decay. in trypanosomatids, mrna degradation is important in controlling the expression of differentially expressed genes. genomic annotation studies have revealed several potential deadenylase ...201121743004
stearoyl-coa desaturase is an essential enzyme for the parasitic protist trypanosoma brucei.trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. to adapt to these changes, the fluidity of its membranes plays a crucial role. this fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. we have previously shown that the oleoyl desaturase is essential for trypanosoma cruzi and t. brucei. in this work, we present experimental support for the relevance of stearoyl ...201121820408
sleeping sickness.human african trypanosomiasis (hat), or sleeping sickness, is a vector-borne disease that flourishes in impoverished, rural parts of sub-saharan africa. it is caused by infection with the protozoan parasite trypanosoma brucei and is transmitted by tsetse flies of the genus glossina. the majority of cases are caused by t. b. gambiense, which gives rise to the chronic, anthroponotic endemic disease in western and central africa. infection with t. b. rhodesiense leads to the acute, zoonotic form of ...201121722252
high affinity nanobodies against the trypanosome brucei vsg are potent trypanolytic agents that block endocytosis.the african trypanosome trypanosoma brucei, which persists within the bloodstream of the mammalian host, has evolved potent mechanisms for immune evasion. specifically, antigenic variation of the variant-specific surface glycoprotein (vsg) and a highly active endocytosis and recycling of the surface coat efficiently delay killing mediated by anti-vsg antibodies. consequently, conventional vsg-specific intact immunoglobulins are non-trypanocidal in the absence of complement. in sharp contrast, mo ...201121698216
optimisation of the anti-trypanosoma brucei activity of the opioid agonist u50488.screening of the sigma-aldrich library of pharmacologically active compounds (lopac) against cultured trypanosoma brucei, the causative agent of african sleeping sickness, resulted in the identification of a number of compounds with selective antiproliferative activity over mammalian cells. these included (+)-(1r,2r)-u50488, a weak opioid agonist with an ec(50) value of 59ôçànm as determined in our t.ôçàbrucei inôçàvitro assay reported previously. this paper describes the modification of key str ...201121834094
in vivo study in trypanosoma brucei links mitochondrial transfer rna import to mitochondrial protein import.trypanosoma brucei imports all mitochondrial transfer rnas (trnas) from the cytosol. by using cell lines that allow independent tetracycline-inducible rna interference and isopropyl-+¦-d-thiogalactopyranoside-inducible expression of a tagged trna, we show that ablation of tim17 and mitochondrial heat-shock protein 70, components of the inner-membrane protein translocation machinery, strongly inhibits import of newly synthesized trnas. these findings, together with previous results in yeast and p ...201121720389
impact of microscopic motility on the swimming behavior of parasites: straighter trypanosomes are more directional.microorganisms, particularly parasites, have developed sophisticated swimming mechanisms to cope with a varied range of environments. african trypanosomes, causative agents of fatal illness in humans and animals, use an insect vector (the tsetse fly) to infect mammals, involving many developmental changes in which cell motility is of prime importance. our studies reveal that differences in cell body shape are correlated with a diverse range of cell behaviors contributing to the directional motio ...201121698122
effect of substrate features and mutagenesis of active site tyrosine residues on the reaction course catalyzed by trypanosoma brucei sterol c24-methyltransferase.trypanosoma brucei (tb) sterol c24-methyl transferase (24-smt) synthesizes an unconventional 24-alkyl sterol product set consisting of ôêå24(25), ôêå24(28)- and ôêå25(27)-olefins. the c-methylation reaction requires si(+¦)-face c24-methyl addition coupled to reversible migration of positive charge from c24 to c25. the hydride shifts responsible for charge migration in formation of multiple ergostane olefin isomers catalyzed by tbsmt were examined by incubation of a series of sterol acceptors pai ...201121736559
oxidative stress protection of trypanosomes requires selenophosphate synthase.selenoproteins are characterized by the incorporation of at least one amino acid selenocysteine (sec-u) encoded by in-frame uga stop codons. these proteins, as well as the components of the sec synthesis pathway, are present in members of the bacteria, archaea and eukaryote domains. although not a ubiquitous pathway in all organisms, it was also identified in several protozoa, including the kinetoplastida. genetic evidence has indicated that the pathway is non-essential to the survival of trypan ...201121723329
protein functional links in trypanosoma brucei, identified by gene fusion analysis.abstract:201121729286
carlina oxide - a natural polyacetylene from carlina acaulis (asteraceae) with potent antitrypanosomal and antimicrobial properties.carlina acaulis (asteraceae) has a long history of medicinal use in europe due to its antimicrobial properties. the strong activity of carlina oxide, the main compound of the essential oil of c. acaulis against two mrsa strains, streptococcus pyogenes, pseudomonas aeruginosa, candida albicans, and c. glabrata was confirmed. a strong and selective activity against trypanosoma brucei brucei with an ic (50) of 1.0ôçë-ág/ml and a si of 446 compared to human hela cells was recorded. the selective tox ...201121678234
cytotoxic activity of secondary metabolites derived from artemisia annua l. towards cancer cells in comparison to its designated active constituent artemisinin.artemisia annua l. (sweet wormwood, qinhao) has traditionally been used in chinese medicine. the isolation of artemisinin from artemisia annua and its worldwide accepted application in malaria therapy is one of the showcase success stories of phytomedicine during the past decades. artemisinin-type compounds are also active towards other protozoal or viral diseases as well as cancer cells in vitro and in vivo. nowadays, artemisia annua tea is used as a self-reliant treatment in developing countri ...201121831619
development of novel drugs for human african trypanosomiasis.human african trypanosomiasis (hat) or 'sleeping sickness' is a neglected tropical disease caused by the parasite trypanosoma brucei. novel models for funding pharmaceutical development against hat are beginning to yield results. the drugs for neglected diseases initiative (dndi) rediscovered a nitroimidazole, fexinidazole, which is currently in phase i clinical trials. novel benzoxaboroles, discovered by anacor, scynexis and dndi, have good pharmacokinetic properties in plasma and in the brain ...201121707314
response to "role of rpb7 in rna pol i transcription in trypanosoma brucei". 201121816182
senna occidentalis leaf extract possesses antitrypanosomal activity and ameliorates the trypanosome-induced anemia and organ damage.the in vitro and in vivo antitrypanosomal effects of the ethanol extract of senna occidentalis leaf were investigated. the crude extract exhibited an in vitro activity against trypanosoma brucei brucei as it completely eliminated parasites' motility within 10 minutes postincubation with 6.66 mg/ml of effective extract concentration. the extract was further used to treat experimentally t. brucei brucei infected rats at concentrations of 100 and 200 mg/kg body weight, beginning on day 5 post infec ...201021808562
comparative genomic analysis of dinucleotide repeats in tritryps.the protozoans trypanosoma cruzi, trypanosoma brucei and leishmania major (tritryps), are evolutionarily ancient eukaryotes which cause worldwide human parasitosis. they present unique biological features. indeed, canonical dna/rna cis-acting elements remain mostly elusive. repetitive sequences, originally considered as selfish dna, have been lately recognized as potentially important functional sequence elements in cell biology. in particular, the dinucleotide patterns have been related to geno ...201121824509
trypanosomatid rack1 orthologs show functional differences associated with translation despite similar roles in leishmania pathogenesis.rack1 proteins belong to the eukaryote wd40-repeat protein family and function as spatial regulators of multiple cellular events, including signaling pathways, the cell cycle and translation. for this latter role, structural and genetic studies indicate that rack1 associates with the ribosome through two conserved positively charged amino acids in its first wd40 domain. unlike rack1s, including trypanosoma brucei rack1 (tbrack1), only one of these two positively-charged residues is conserved in ...201121677780
convolutamines i and j, antitrypanosomal alkaloids from the bryozoan amathia tortusa.mass-directed isolation of the ch(2)cl(2)/ch(3)oh extract from the marine bryozoan amathia tortusa resulted in the purification of two new brominated alkaloids, convolutamines i (1) and j (2). the structures of 1 and 2 were determined following spectroscopic data analysis. both compounds were isolated during a drug discovery program aimed at identifying new antitrypanosomal leads from a prefractionated natural product library. compounds 1 and 2 were shown to be active toward the parasite trypano ...201121705225
t. brucei infection reduces b lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional b-cell apoptosis.african trypanosomes of the trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease african trypanosomiasis in humans and contribute to the animal counterpart, nagana. trypanosome clearance from the bloodstream is mediated by antibodies specific for their variant surface glycoprotein (vsg) coat antigens. however, t. brucei infection induces polyclonal b cell activation, b cell clonal exhaustion, sustained depletion of mature splenic marginal zone b (mzb) an ...201121738467
gene expression in trypanosoma brucei: lessons from high-throughput rna sequencing.trypanosoma brucei undergoes major biochemical and morphological changes during its development from the bloodstream form in the mammalian host to the procyclic form in the midgut of its insect host. the underlying regulation of gene expression, however, is poorly understood. more than 60% of the predicted genes remain annotated as hypothetical, and the 5' and 3' untranslated regions important for regulation of gene expression are unknown for >90% of the genes. in this review, we compare the dat ...201121737348
in vitro antitrypanosomal activity of plant terpenes against trypanosoma brucei.during the course of screening to discover antitrypanosomal compounds, 24 known plant terpenes (6 sesquiterpenes, 14 sesquiterpene lactones and 4 diterpenes) were evaluated for in vitro antitrypanosomal activity against trypanosoma brucei brucei. among them, 22 terpenes exhibited antitrypanosomal activity. in particular, +¦-eudesmol, hinesol, nardosinone and 4-peroxy-1,2,4,5-tetrahydro-+¦-santonin all exhibited selective and potent antitrypanosomal activities in vitro. detailed here in an in vit ...201121843897
role of rpb7 in rna pol i transcription in trypanosoma brucei. 201121816180
activation and inhibition of ctp synthase from trypanosoma brucei, the causative agent of african sleeping sickness.ctp synthase from trypanosoma brucei (tbctps) catalyzes the conversion of utp to ctp and is a recognized target for the development of antiprotozoal agents. gtp activates glutamine-dependent ctp formation catalyzed by tbctps at concentrations below 0.2mm, but inhibits this activity at concentrations above 0.2mm. tbctps catalyzes ammonia-dependent ctp formation, which is inhibited by purine derivatives such as gtp, guanosine, caffeine, and uric acid with ic(50) values of 460, 380, 480, and 100++m ...201121840216
transcription by the multifunctional rna polymerase i in trypanosoma brucei functions independently of rpb7.trypanosoma brucei has a multifunctional rna polymerase (pol) i that transcribes ribosomal gene units (rrna) and units encoding its major cell surface proteins variant surface glycoprotein (vsg) and procyclin. previous analysis of tandem affinity-purified, transcriptionally active rna pol i identified ten subunits including an apparently trypanosomatid-specific protein termed rpa31. another ortholog was identified in silico. no orthologs of the yeast subunit doublet rpa43/rpa14 have been identif ...201121816181
Structure of Trypanosoma brucei flagellum accounts for its bihelical motion.Trypanosoma brucei is a parasitic protozoan that causes African sleeping sickness. It contains a flagellum required for locomotion and viability. In addition to a microtubular axoneme, the flagellum contains a crystalline paraflagellar rod (PFR) and connecting proteins. We show here, by cryoelectron tomography, the structure of the flagellum in three bending states. The PFR lattice in straight flagella repeats every 56 nm along the length of the axoneme, matching the spacing of the connecting pr ...201121690369
phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite.protozoan infections remain a major unsolved medical problem in many parts of our world. a major obstacle to their treatment is the blatant lack of medication that is affordable, effective, safe and easy to administer. for some of these diseases, including human sleeping sickness, very few compounds are available, many of them old and all of them fraught with toxic side effects. we explore a new concept for developing new-generation antiprotozoan drugs that are based on phosphodiesterase (pde) i ...201121859303
post eclosion age predicts the prevalence of midgut trypanosome infections in glossina.the teneral phenomenon, as observed in glossina sp., refers to the increased susceptibility of the fly to trypanosome infection when the first bloodmeal taken is trypanosome-infected. in recent years, the term teneral has gradually become synonymous with unfed, and thus fails to consider the age of the newly emerged fly at the time the first bloodmeal is taken. furthermore, conflicting evidence exists of the effect of the age of the teneral fly post eclosion when it is given the infected first b ...201122087240
New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents.In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(ii) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray di ...201122138896
Trypanosoma brucei brucei oligopeptidase B null mutants display increased prolyl oligopeptidase-like activity.African trypanosomosis is a parasitic disease in man and animals caused by protozoan parasites of the genus Trypanosoma. Nagana, the cattle form of the disease, is caused by Trypanosoma congolense, Trypanosoma vivax and Trypanosoma brucei brucei. An option for developing vaccines and chemotherapeutic agents against trypanosomosis is to target pathogenic factors released by the parasite during infection, namely an "anti-disease" approach. One such pathogenic factor is oligopeptidase B (TbOPB), a ...201122123425
The role of the 5'-3' exoribonuclease XRNA in transcriptome-wide mRNA degradation.The steady-state level of each mRNA in a cell is a balance between synthesis and degradation. Here, we use high-throughput RNA sequencing (RNASeq) to determine the relationship between mRNA degradation and mRNA abundance on a transcriptome-wide scale. The model organism used was the bloodstream form of Trypanosoma brucei, a protist that lacks regulation of RNA polymerase II initiation. The mRNA half-lives varied over two orders of magnitude, with a median half-life of 13 min for total (rRNA-depl ...201121947264
Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis.Human African trypanosomiasis, caused by the kinetoplastid parasite Trypanosoma brucei, affects thousands of people across sub-Saharan Africa, and is fatal if left untreated. Treatment options for this disease, particularly stage 2 disease, which occurs after parasites have infected brain tissue, are limited due to inadequate efficacy, toxicity and the complexity of treatment regimens. We have discovered and optimized a series of benzoxaborole-6-carboxamides to provide trypanocidal compounds tha ...201121859301
The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing.Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the kinetoplastid parasites Trypanosoma brucei, T. cruzi, Leishmania major, and L. donovani. The genomes of trypanosomatids enco ...201121886855
biological activities of xanthatin from xanthium strumarium leaves.the objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from xanthium strumarium (asteraceae) leaves. inhibition of bloodstream forms of trypanosoma brucei brucei and leukaemia hl-60 cell proliferation was assessed using resazurin as a vital stain. xanthatin was found to be the major and most active compound against t. b. brucei with an ic(50) value of 2.63 µg/ml and a selectivity index of 20. the possible mode o ...201121953905
distinct toll-like receptor signals regulate cerebral parasite load and interferon α/β and tumor necrosis factor α-dependent t-cell infiltration in the brains of trypanosoma brucei-infected mice.background. the penetration of t cells and trypanosomes into the brain parenchyma is a major pathogenetic event in african trypanosomiasis. methods. the role of innate immune responses in the penetration of t cells and trypanosoma brucei brucei into the brain was studied in knockout mice by using double immunofluorescent staining and real-time polymerase chain reaction. results. we demonstrate that toll-like receptor (tlr)-myd88-mediated signaling is required for t-cell and parasite penetration ...201222116836
target repurposing for neglected diseases.infectious diseases are an enormous burden to global health and ,since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug-discovery efforts. therefore, pragmatic means by which new therapeutics can be discovered are needed. one such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. in many cases, the medicinal c ...201121859304
trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor.metacaspases are caspase family cysteine peptidases found in plants, fungi, and protozoa but not mammals. trypanosoma brucei is unusual in having five metacaspases (mca1-mca5), of which mca1 and mca4 have active site substitutions, making them possible non-enzymatic homologues. here we demonstrate that recombinant mca4 lacks detectable peptidase activity despite maintaining a functional peptidase structure. mca4 is expressed primarily in the bloodstream form of the parasite and associates with t ...201121949125
3-(3-amino-3-carboxypropyl)-5,6-dihydrouridine is one of two novel post-transcriptional modifications in trnalys(uuu) from trypanosoma brucei.trna is the most heavily modified of all rna types, with typically 10-20% of the residues being post-transcriptionally altered. unravelling the modification pattern of a trna is a challenging task; there are 92 currently known trna modifications, many of which are chemically similar. furthermore, the trna has to be investigated with single-nucleotide resolution in order to ensure complete mapping of all modifications. in the present work, we characterized trna(lys)(uuu) from trypanosoma brucei, ...201122040320
antiparasitic prodrug nifurtimox: revisiting its activation mechanism.evaluation of: hall bs, bot c, wilkinson sr. nifurtimox activation by trypanosomal type i nitroreductases generates cytotoxic nitrile metabolites. j. biol. chem. 286, 13088-13095 (2011). the prodrug nifurtimox has been one of the pharmacologic alternatives to treat chagas disease and currently forms part of a combinational therapy to treat west african trypanosomiasis. despite this, nifurtimox's mechanism of action is only partially understood and has been related to induction of oxidative stres ...201121861617
in vitro antileishmanial and antitrypanosomal activities of five medicinal plants from burkina faso.after ethnobotanical surveys in central and western regions of burkina faso, five plants namely lantana ukambensis (verbenaceae), xeoderris sthulmannii (fabaceae), parinari curatellifollia (chrysobalanaceae), ozoroa insignis (anacardiaceae), and ficus platyphylla (moraceae) were selected for their traditional use in the treatment of parasitic diseases and cancer. our previous studies have focused on the phytochemical, genotoxicity, antioxidant, and antiproliferative activities of these plants. i ...201122037827
non-linear modeling of 1h nmr metabonomic data using kernel-based orthogonal projections to latent structures optimized by simulated annealing.linear multivariate projection methods are frequently applied for predictive modeling of spectroscopic data in metabonomic studies. the opls method is a commonly used computational procedure for characterizing spectral metabonomic data, largely due to its favorable model interpretation properties providing separate descriptions of predictive variation and response-orthogonal structured noise. however, when the relationship between descriptor variables and the response is non-linear, conventional ...201121962350
mechanism for activation of triosephosphate isomerase by phosphite dianion: the role of a ligand-driven conformational change.the l232a mutation in triosephosphate isomerase (tim) from trypanosoma brucei brucei results in a small 6-fold decrease in k(cat)/k(m) for the reversible enzyme-catalyzed isomerization of glyceraldehyde 3-phosphate to give dihydroxyacetone phosphate. in contrast, this mutation leads to a 17-fold increase in the second-order rate constant for the tim-catalyzed proton transfer reaction of the truncated substrate piece [1-(13)c]glycolaldehyde ([1-(13)c]-ga) in d(2)o, a 25-fold increase in the thi ...201121939233
Identification of a second catalytically active trans-sialidase in Trypanosoma brucei.The procyclic stage of Trypanosoma brucei is covered by glycosylphosphatidylinositol (GPI)-anchored surface proteins called procyclins. The procyclin GPI anchor contains a side chain of N-acetyllactosamine repeats terminated by sialic acids. Sialic acid modification is mediated by trans-sialidases expressed on the parasite's cell surface. Previous studies suggested the presence of more than one active trans-sialidases, but only one has so far been reported. Here we cloned and examined enzyme act ...201122040733
Tandem repeat protein as potential diagnostic antigen for Trypanosoma evansi infection.Trypanosoma evansi infection (surra) causes significant losses in livestock production in tropical and sub-tropical areas. The current ELISA recommended by OIE for diagnosis of the disease is based on trypanosome lysate antigen. However, antigenic variation and unstable nature of cell lysate antigen make it difficult to standardize the assay. Thus, there are needs to develop recombinant antigen-based ELISA that improve stability, sensitivity, and specificity of the test. Since tandem repeat (TR) ...201121927872
in vitro antitrypanosomal activity of bis(bibenzyls)s and bibenzyls from liverworts against trypanosoma brucei.during the course of our screening program to discover new antitrypanosomal compounds, 17 known plant aromatic compounds [12 bis(bibenzyls)s and 5 bibenzyls] were evaluated for in vitro activity against trypanosoma brucei brucei. sixteen compounds were found to exhibit antitrypanosomal activity. in particular, three compounds, marchantin a (1), plagiochin a (5) and 2(r)-2-isopropenyl-6,7-dihydroxy-4-(2-phenylethyl)dihydrobenzofuran (16) demonstrated moderate selective and potent antitrypanosomal ...201121922219
Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution comp ...201121851087
in vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from fijian kawa (piper methysticum).during our search to discover new antitrypanosomal compounds, eight known plant compounds (three phenolic compounds and five kawa lactones) were evaluated for in vitro activity against trypanosoma brucei brucei. among them, we found two phenolic compounds and three kawa lactones possessing an α-pyrone influenced antitrypanosomal property. in particular, β-phenethyl caffeate, farnesyl caffeate and dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity in vitro. we ...201122116743
adaptor protein-3 (ap-3) complex mediates the biogenesis of acidocalcisomes and is essential for growth and virulence of trypanosoma brucei.acidocalcisomes are acidic calcium and polyphosphate storage organelles found in a diverse range of organisms. here we present evidence that the biogenesis of acidocalcisomes in trypanosoma brucei is linked to the expression of adaptor protein-3 (ap-3) complex. localization studies in cell lines expressing β3 and δ subunits of ap-3 fused to epitope tags revealed their partial co-localization with the vacuolar proton pyrophosphatase, a marker of acidocalcisomes, with the golgi marker golgi reasse ...201121880705
analysis of blood-brain barrier permeability of monovalent nanobodies using microdialysis.background and purpose:  nanobodies are promising antigen-binding moieties for molecular imaging and therapeutic purposes due to their favorable pharmacological and pharmacokinetic properties. however, the capability of monovalent nanobodies to reach targets in the central nervous system (cns) remains to be demonstrated. experimental aproach:  we have assessed the blood-brain barrier permeability of nb_an33, a nanobody against the trypanosoma brucei brucei variant-specific surface glycoprotein ( ...201122013955
melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human african trypanosomiasis.human african trypanosomiasis (hat), or sleeping sickness, results from infection with the protozoan parasites trypanosoma brucei (t. b.) gambiense or t. b. rhodesiense and is invariably fatal if untreated. there are 60 million people at risk from the disease throughout sub-saharan africa. the infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (cns) to ca ...201121909447
semi-targeted analysis of metabolites using capillary-flow ion chromatography coupled to high-resolution mass spectrometry.this work describes a novel application of capillary-flow ion chromatography mass spectrometry for metabolomic analysis, and comparison of the technique to octadecyl silica and hydrophilic interaction chromatography (hilic)-based mass spectrometry. while liquid chromatography/mass spectrometry (lc/ms) is rapidly becoming the standard technique for metabolomic analysis, metabolomic samples are extremely heterogeneous, leading to a requirement for multiple methods of analysis and separation techni ...201122002700
Amino acid determinants of substrate selectivity in the Trypanosoma brucei sphingolipid synthase family.The substrate selectivity of four Trypanosoma brucei sphingolipid synthases was examined. TbSLS1, an inositol phosphorylceramide (IPC) synthase, and TbSLS4, a bifunctional sphingomyelin (SM)/ethanolamine phosphorylceramide (EPC) synthase, were inactivated by Ala substitutions of a conserved triad of residues His210, His253, and Asp257 thought to form part of the active site. TbSLS4 also catalyzed the reverse reaction, production of ceramide from sphingomyelin, but none of the Ala substitutions o ...201121899277
in vivo antitrypanosomal effects of some ethnomedicinal plants from nupeland of north central nigeria.four medicinal plants acacia nilotica, bombax buonopozense, terminalia avicennioides and zanthoxylum zanthoxyloides traditionally used for treatment of sleeping sickness in nupeland were investigated for in vivo antitrypanosomal activity. methanol extracts of different parts of each plant (stem barks and fruits) were obtained and evaluated for their in vivo antitrypanosomal activities against trypanosoma brucei brucei. phytochemical screening of the methanol extracts of each plant were performed ...201122238478
trypanocidal and cytotoxic effects of 30 ethiopian medicinal plants.trypanocidal and cytotoxic effects of traditionally used medicinal plants of ethiopia were evaluated. a total of 60 crude plant extracts were prepared from 30 plant species using ch2cl2 and meoh. effect upon cell proliferation by the extracts, for both bloodstream forms of trypanosoma brucei brucei and human leukaemia hl-60 cells, was assessed using resazurin as vital stain. of all ch2cl2 and meoh extracts evaluated against the trypanosomes, the ch2cl2 extracts from five plants showed trypanocid ...201122351978
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 ...201122226682
structures of adenosine kinase from trypanosoma brucei brucei.trypanosoma brucei is a single-cellular parasite of the genus kinetoplastida and is the causative agent of african sleeping sickness in humans. adenosine kinase is a key enzyme in the purine-salvage pathway, phosphorylating adenosine to amp, and also activates cytotoxic analogues such as cordycepin and ara-a by their phosphorylation. the structures of t. brucei brucei adenosine kinase (tbak) in its unliganded open conformation and complexed with adenosine and adp in the closed conformation are b ...201324419613
antibacterial efficacy of recombinant siganus oramin l-amino acid oxidase expressed in pichia pastoris.siganus oraminl-amino acid oxidase is a novel natural protein (named sr-laao) isolated from serum of the rabbitfish (s. oramin), which showed antibacterial activity against both gram-positive and gram-negative bacteria and had a lethal effect on the parasites cryptocaryon irritans, trypanosoma brucei brucei and ichthyophthirius multifiliis. in order to test whether recombinant sr-laao (rsr-laao) produced by the eukaryotic expression system also has antimicrobial activity, the yeast pichia pastor ...201425238719
chemical profiling of the essential oils of syzygium aqueum, syzygium samarangense and eugenia uniflora and their discrimination using chemometric analysis.the essential oil compositions of the leaves of three related myrtaceae species, namely syzygium aqueum, syzygium samarangense and eugenia uniflora, were investigated using glc/ms and glc/fid. altogether, 125 compounds were identified: α-selinene (13.85%), β-caryophyllene (12.72%) and β-selinene constitute the most abundant constituents in s. aqueum. germacrene d (21.62%) represents the major compound in s. samarangense whereas in e. uniflora, spathulenol (15.80%) represents the predominant comp ...201627447784
new glycosides and trypanocidal metabolites from vangueria edulis.a new iridoid glucoside, 10-methoxy apodanthoside (1), and a new monoterpene glycoside, (3s,6s)-cis linalool-3,7-oxide o-β-d-glucopyranosyl-(1"-->5')-β-d- xylofuranoside (2), were isolated from v. edulis (rubiaceae), along with eighteen known compounds (3-20), including monoterpenes, iridoid glycosides, and a lignin, which were encountered for the first time in the genus vangueria,. the structural elucidation of the isolates was based on the analysis of spectroscopic (1d and 2d nmr) and hr-esi-m ...201526749819
improved anticancer and antiparasitic activity of new lawsone mannich bases.substituted lawsone mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. the new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ros formation. in addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic trypanosoma brucei brucei cells via deformation of ...201727912173
in vitro trypanocidal activity of antibodies to bacterially expressed trypanosoma brucei tubulin.there are only four drugs for treating african trypanosomiasis, a devastating disease in sub-saharan africa. with slow discovery of better drugs, vaccination is viewed as the best method of control. we previously showed that antibodies to native trypanosoma brucei brucei tubulin inhibit the growth of trypanosomes in culture. here, we aimed to determine the effect of antibodies to bacterially expressed trypanosome tubulin on t. brucei brucei growth.201223109963
metabolomics-guided isolation of anti-trypanosomal metabolites from the endophytic fungus lasiodiplodia theobromae.fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. the application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. in this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for ...201627760442
antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.a small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. all tested compounds were active or moderately active against trypanosoma cruzi amastigotes in infected l6 cells and trypanosoma brucei brucei, four of eleven compounds were moderately active against leishmania donovani axenic parasites while none were deemed active against t. brucei rhodesiense. for the mo ...201627092415
bioactive phloroglucinols from mallotus oppositifolius.the two new acylphloroglucinol derivatives, methylene-bis-aspidinol ab (1) and mallopposinol (2), together with the nine known compounds, aspidinol b (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of mallotus oppositifolius. their structures were elucidated by spectral analysis including ms, 1d and 2d-nmr spectroscopy. in vitro trypanocidal and antileishmanial acti ...201526463755
"squalenoylcurcumin" nanoassemblies as water-dispersible drug candidates with antileishmanial activity.curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. the molecule is well tolerated in humans. however, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. new derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1',2-tris-norsqualenic acid. these "squalenoylcurcumins" were formulated as water-d ...201525523035
antiprotozoal activities of millettia richardiana (fabaceae) from madagascar.with at least 60% of the millettia species (fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of millettia richardiana. water and methanol crude extracts of the stem barks from m. richardiana and the six fractions resulting from the fractionation of the methanol extract were tested. the dichloromethane extracted fraction showed the best in vitro antiprotozoal activities (ic50=5.8 μg/ml against plasmodium falciparum, 11.8 μg/ml ...201424705564
synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.importance of heme in african trypanosomes, leishmania sp. and plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. consequently, twenty-four porphyrin precursors and derivatives were evaluated against leishmania donovani, trypanosoma brucei and plasmodium sp. the best active compound against trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, wit ...201323851117
3-(oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid trypanosoma brucei, the causative agent for human african trypanosomiasis.a whole organism high-throughput screen of approximately 87,000 compounds against trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. herein we report a structure-activity relationship (sar) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]pyridin-2-yl)anilides. sharp sar is revealed, with our most active compound (5) exhibiting an ic₅ ...201323831695
antiprotozoal activity of khaya anthotheca, (welv.) c.d.c. a plant used by chimpanzees for self-medication.khaya species, endemic to africa and madagascar, continues to be valuable in indigenous traditional medicine. their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. in the budongo rain forest of western uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed.201323501156
8,8-dialkyldihydroberberines with potent antiprotozoal activity.semisynthetic 8,8-dialkyldihydroberberines (8,8-ddbs) were found to possess mid- to low-nanomolar potency against plasmodium falciparum blood-stage parasites, leishmania donovani intracellular amastigotes, and trypanosoma brucei brucei bloodstream forms. for example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro ic50 values of 77, 100, and 5.3 nm against these three parasites, respectively. in turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-ddbs, wer ...201323167812
novel 3-nitro-1h-1,2,4-triazole-based amides and sulfonamides as potential antitrypanosomal agents.a series of novel 3-nitro-1h-1,2,4-triazole-based (and in some cases 2-nitro-1h-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. out of 36 compounds tested, 29 (mostly 3-nitro-1h-1,2,4-triazoles) displayed significant activity against trypanosoma cruzi intracellular amastigotes (ic(50) ranging from 28 nm to 3.72 μm) without concomitant toxicity to l6 host cells (selectivity 66-2782). twen ...201222550999
synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives.a new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against leishmania donovani and trypanosoma brucei brucei. results from these structure-activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against l. donovani promastigotes and amastigotes parasites (ic(50) values in a range of 2-11 μm). additionally, compound 3b has emerged from this study as the most active compound in the serie ...201222472166
in vitro antiprotozoal activity and cytotoxicity of extracts and isolated constituents from greenwayodendron suaveolens.the nkundo people (nkundo area of bolongo, mai-ndombe district, bandundu province, dr congo) use various plant parts of the tree greenwayodendron suaveolens (engl. & diels) verdc. (syn. polyalthia suaveolens engl. & diels) (annonaceae) against malaria, but its antiprotozoal constituents are not known.201627693770
in vitro antiprotozoal activity and cytotoxicity of extracts and fractions from the leaves, root bark and stem bark of isolona hexaloba.isolona hexaloba (pierre) engl. and diels (annonaceae) is traditionally used in d.r. congo against parasitic diseases including malaria.201526239153
in vitro antiprotozoal and cytotoxic activity of ethnopharmacologically selected guinean plants.based on an ethnobotanical survey, 41 guinean plant species widely used in the traditional treatment of fever and/or malaria were collected. from these, 74 polar and apolar extracts were prepared and tested for their in vitro antiprotozoal activity along with their cytotoxicity on mrc-5 cells. a potent activity (ic50 < 5 µg/ml) was observed for terminalia albida, vismia guineensis, spondias mombin, and pavetta crassipes against plasmodium falciparum; for pavetta crassipes, vismia guineensis, gui ...201425180493
synthesis and in vitro evaluation of tropane halogenated-derivatives against malaria, sleeping sickness, chagas disease and leishmaniasis.a series of twelve analogs carrying fluoro, chloro, bromo and iodo halogens on the ortho, meta and para positions of a benzoyloxytropane skeleton were synthesized by a simple acylation of 8-methyl-8-aza-bicyclo[3.2.1]octan- 3α-ol by halogenobenzoyl chlorides. the compounds were evaluated in vitro against plasmodium falciparum (p. f.), trypanosoma brucei brucei (t. b. b.), trypanosoma cruzi (t. c.) and leishmania infantum (l. i.). this study shows that the presence of a halogenated atom and its p ...201424813684
antiprotozoal screening and cytotoxicity of extracts and fractions from the leaves, stem bark and root bark of alstonia congensis.to evaluate the antiprotozoal activity and cytotoxicity of extracts and fractions from the leaves, root bark and stem bark of alstonia congensis (apocynaceae), used in traditional medicine against parasitic diseases.201323612422
dereplication strategies for targeted isolation of new antitrypanosomal actinosporins a and b from a marine sponge associated-actinokineospora sp. eg49.high resolution fourier transform mass spectrometry (hrftms) and nuclear magnetic resonance (nmr) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium actinokineospora sp. eg49 extract. principal component (pca), hierarchical clustering (hca), and orthogonal partial least square-discriminant analysis (opls-da) were used to evaluate the hrftms and nmr data of crude extracts from four ...201424663112
antitrypanosomal compounds from the essential oil and extracts of keetia leucantha leaves with inhibitor activity on trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.keetia leucantha is a west african tree used in traditional medicine to treat several diseases among which parasitic infections. the dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on plasmodium falciparum, trypanosoma brucei brucei and leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (bero et al. 2009, 2011). in continuation of our investigations on the antitrypanosomal compounds from this dichlorome ...201323312849
antiparasitic activities of two sesquiterpenic lactones isolated from acanthospermum hispidum d.c.aerial parts of acanthospermum hispidum d.c. are often used by traditional healers in benin for various diseases and especially for malaria.201222440261
biological characterization of chemically diverse compounds targeting the plasmodium falciparum coenzyme a synthesis pathway.in the fight against malaria, the discovery of chemical compounds with a novel mode of action and/or chemistry distinct from currently used drugs is vital to counteract the parasite's known ability to develop drug resistance. another desirable aspect is efficacy against gametocytes, the sexual developmental stage of the parasite which enables the transmission through anopheles vectors. using a chemical rescue approach, we previously identified compounds targeting plasmodium falciparum coenzyme a ...201627855724
performance of microscopy for the diagnosis of malaria and human african trypanosomiasis by diagnostic laboratories in the democratic republic of the congo: results of a nation-wide external quality assessment.the present external quality assessment (eqa) assessed microscopy of blood parasites among diagnostic laboratories in the democratic republic of the congo. the eqa addressed 445 participants in 10/11 provinces (october 2013-april 2014). participants were sent a panel of five slides and asked to return a routinely stained slide which was assessed for quality of preparation and staining. response rate was 89.9% (400/445). for slide 1 (no parasites), 30.6% participants reported malaria, mostly plas ...201626788725
profiling the anti-protozoal activity of anti-cancer hdac inhibitors against plasmodium and trypanosoma parasites.histone deacetylase (hdac) enzymes work together with histone acetyltransferases (hats) to reversibly acetylate both histone and non-histone proteins. as a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. hdacs are validated drug targets for some types of cancer, with four hdac inhibitors clinically approved. however, they are also showing promise as novel drug targets for other indications, including malaria ...201526199860
design and synthesis of a screening library using the natural product scaffold 3-chloro-4-hydroxyphenylacetic acid.the fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (1) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. a 20-membered amide library (3-22) was generated by first converting 1 to methyl (3-chloro-4-hydroxyphenyl)acetate (2), then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. the structures of the synthetic analogues (3-22) were elucidated by spectroscopic data analysis. ...201525803573
in vitro antitrypanosomal and antiplasmodial activities of crude extracts and essential oils of ocimum gratissimum linn from benin and influence of vegetative stage.different parts of ocimum gratissimum linn are largely used in folk medicine for the treatment of many diseases, some of which related to parasitical infections as fevers and headaches. in order to validate their use and to clarify the plant part which possesses the best antiparasitic properties, we decided to evaluate the in vitro antiplasmodial and antitrypanosomal activities of essential oils and crude extracts from leaves, stems and seeds of ocimum gratissimum as well as their cytotoxicity.201425058875
design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents--part iii.a series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine b and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed suzuki-miyaura cross-coupling reactions. these new compounds were tested for in vitro antiparasitic activity upon three leishmania spp. strains. biological results showed activity against the promastigote forms of l. major, l. mexicana and l ...201424858543
chemical composition, cytotoxicity and in vitro antitrypanosomal and antiplasmodial activity of the essential oils of four cymbopogon species from benin.cymbopogon species are largely used in folk medicine for the treatment of many diseases some of which related to parasitical diseases as fevers and headaches. as part of our research on antiparasitic essential oils from beninese plants, we decided to evaluate the in vitro antiplasmodial and antitrypanosomal activities of essential oils of four cymbopogon species used in traditional medicine as well as their cytotoxicity.201424269775
approaches to protozoan drug discovery: phenotypic screening.determining the activity of a compound and the potential impact on a diseased state is frequently undertaken using phenotypic or target-based approaches. phenotypic screens have the advantage of the whole organism being exposed to the compound and thus all the targets and biological pathways associated with it. cell penetration and access to targets in their "natural" environment are taken into account. unless utilizing a genetically modified organism with an additional target associated indicat ...201323927763
membrane active chelators as novel anti-african trypanosome and anti-malarial drugs.malaria (plasmodium spp.) and human african trypanosomiasis (trypanosoma brucei spp.) are vector borne, deadly parasitic diseases. while chemotherapeutic agents for both diseases are available, difficulty in disease eradication and development of drug resistance require that new therapies targeting unexplored pathways or exploiting novel modes of action be developed. intracellular plasmodium and extracellular trypanosoma brucei may have unique and essential requirements for divalent metal ions, ...201323811202
albopunctatone, an antiplasmodial anthrone-anthraquinone from the australian ascidian didemnum albopunctatum.chemical investigation of a meoh extract of the great barrier reef ascidian didemnum albopunctatum has led to the isolation and identification of a new anthrone-anthraquinone, albopunctatone (1), together with the known 1,8-dihydroxy-9,10-anthraquinone (2). the structure of 1 was established from interpretation of 1d and 2d nmr spectroscopic and mass spectrometric data. the compounds were screened for antiplasmodial activity against chloroquine-resistant and -sensitive strains of the malaria par ...201222680914
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