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the in vitro biological activity of the brazilian brown seaweed dictyota mertensii against leishmania amazonensis.seaweeds present a wide variety of interesting bioactive molecules. in the present work we evaluated the biological activity of the dichloromethane/methanol (2:1) extract (dme) from the brown seaweed dictyota mertensii against leishmania amazonensis and its cytotoxic potential on mammalian cells. the extract showed significant inhibitory effect on the growth of promastigote forms (ic50=71.60 μg/ml) and low toxicity against mammalian cells (cc50=233.10 μg/ml). the dme was also efficient in inhibi ...201425207712
furofuran lignans display schistosomicidal and trypanocidal activities.parasitic diseases continue to be a major worldwide health problem, and there is an urgent need for development of therapeutic drugs. this paper describes synthesis of dehydrodiferulic acid dilactone 1 and dehydrodisinapic acid dilactone 2 furofuran lignans by oxidative coupling of ferulic and sinapic acids, respectively. their schistosomicidal, trypanocidal, and leishmanicidal activities were evaluated in vitro against schistosoma mansoni adult worms, trypomastigote and amastigotes forms of try ...201425200100
an in vitro model of antibody-enhanced killing of the intracellular parasite leishmania amazonensis.footpad infection of c3heb/fej mice with leishmania amazonensis leads to chronic lesions accompanied by large parasite loads. co-infecting these animals with l. major leads to induction of an effective th1 immune response that can resolve these lesions. this cross-protection can be recapitulated in vitro by using immune cells from l. major-infected animals to effectively activate l. amazonensis-infected macrophages to kill the parasite. we have shown previously that the b cell population and the ...201425191842
leishmania amazonensis: increase in ecto-atpase activity and parasite burden of vinblastine-resistant protozoa.leishmania amazonensis is a protozoan parasite that induces mucocutaneous and diffuse cutaneous lesions upon infection. an important component in treatment failure is the emergence of drug-resistant parasites. it is necessary to clarify the mechanism of resistance that occurs in these parasites to develop effective drugs for leishmaniasis treatment. promastigote forms of l. amazonensis were selected by gradually increasing concentrations of vinblastine and were maintained under continuous drug p ...201425176449
leishmania amazonensis infection impairs dendritic cell migration from the inflammatory site to the draining lymph node.in vitro studies show that leishmania infection decreases the adhesion of inflammatory phagocytes to connective tissue by a mechanism dependent on the modulation of integrin function. however, we know little about the influence of this reduction in leukocyte adhesion on parasite dissemination from the infection site.201425142021
antileishmanial activity of medicinal plants used in endemic areas in northeastern brazil.this study investigates the leishmanicidal activity of five species of plants used in folk medicine in endemic areas of the state of alagoas, brazil. data were collected in the cities of colonia leopoldina, novo lino, and união dos palmares, alagoas state, from patients with cutaneous leishmaniasis (leishmania amazonensis) who use medicinal plants to treat this disease. plants extracts were tested at a concentration of 1-100 μg/ml in all experiments, except in an assay to evaluate activity again ...201425126099
an optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin b and is effective in treating tegumentary leishmaniasis.amphotericin b (ampb) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. in this study, a nanoparticles-delivery system for ampb (nqc-ampb), containing chitosan and chondroitin sulfate molecules, was evaluated in balb/c mice against leishmania amazonensis. an in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of ampb. nanoparticles were radiolabeled with technetium-99m and ...201425429219
leishmania braziliensis replication protein a subunit 1: molecular modelling, protein expression and analysis of its affinity for both dna and rna.replication factor a (rpa) is a single-strand dna binding protein involved in dna replication, recombination and repair processes. it is composed by the subunits rpa-1, rpa-2 and rpa-3; the major dna-binding activity resides in the subunit 1 of the heterotrimeric rpa complex. in yeast and higher eukaryotes, besides the three basic structural dna-binding domains, the rpa-1 subunit contains an n-terminal region involved in protein-protein interactions with a fourth dna-binding domain. remarkably, ...201425498946
rpa-1 from leishmania amazonensis (larpa-1) structurally differs from other eukaryote rpa-1 and interacts with telomeric dna via its n-terminal ob-fold domain.replication protein a-1 (rpa-1) is a single-stranded dna-binding protein involved in dna metabolism. we previously demonstrated the interaction between larpa-1 and telomeric dna. here, we expressed and purified truncated mutants of larpa-1 and used circular dichroism measurements and molecular dynamics simulations to demonstrate that the tertiary structure of larpa-1 differs from human and yeast rpa-1. larpa-1 interacts with telomeric ssdna via its n-terminal ob-fold domain, whereas rpa from hig ...201425451229
understanding the mechanisms controlling leishmania amazonensis infection in vitro: the role of ltb4 derived from human neutrophils.neutrophils are rapidly recruited to the site of leishmania infection and play an active role in capturing and killing parasites. they are the main source of leukotriene b4 (ltb4), a potent proinflammatory lipid mediator. however, the role of ltb4 in neutrophil infection by leishmania amazonensis is not clear. in this study, we show that l. amazonensis or its lipophosphoglycan can induce neutrophil activation, degranulation, and ltb4 production. using pharmacological inhibitors of leukotriene sy ...201424634497
novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system.the study reported here aimed to develop an optimized nanoparticle delivery system for amphotericin b (ampb) using a polyelectrolyte complexation technique. for this, two oppositely charged polymers presenting anti-leishmanial activity - chitosan (cs) and chondroitin sulfate (chs) - were used: cs as a positively charged polymer and chs as a negatively charged polymer. the chitosan (nq) nanoparticles, chitosan-chondroitin sulfate (nqc) nanoparticles, and chitosan-chondroitin sulfate-amphotericin ...201424627630
identification and characterization of new leishmania promastigote surface antigens, lapsa-38s and lipsa-50s, as major immunodominant excreted/secreted components of l. amazonensis and l. infantum.we have previously demonstrated that sera from dogs vaccinated with excreted/secreted antigens (esa) of leishmania infantum promastigotes (liesap) mainly recognized an immunodominant antigen of 54 kda. an anti-liesap-specific igg2 humoral response was observed and associated to th1-type response in vaccinated dogs. this response was highly correlated with a long-lasting and strong liesap-vaccine protection toward l. infantum experimental infection. in addition, it was also shown that dogs from t ...201424614507
miltefosine increases lipid and protein dynamics in leishmania amazonensis membranes at concentrations similar to those needed for cytotoxicity activity.miltefosine (mt) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. electron paramagnetic resonance (epr) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane of leishmania promastigotes showed that mt causes dramatic increases in membrane dynamics. although these alterations can be detected using a spin-labeled ...201424614380
combination therapy with tamoxifen and amphotericin b in experimental cutaneous leishmaniasis.leishmaniasis chemotherapy remains very challenging. the high cost of active drugs, along with the severity of their side effects and the increasing failure rate of the current therapeutic schemes, calls for the discovery of new active drugs and schemes of treatment. the use of combination therapy has gained much attention in recent years as a possible strategy for overcoming the various shortcomings in the present arsenal. we recently described the effectiveness of tamoxifen in murine models of ...201424550333
potential therapeutic use of herbal extracts in trypanosomiasis.the aim of the present study was to evaluate the effects of crude extracts from handroanthus impetiginosa, ageratum conyzoides, and ruta graveolens on leishmania amazonensis and trypanosoma cruzi infection in vitro. the results showed that the extracts caused significant toxicity in promastigotes and trypomastigotes. a significant decrease in the rate of cell invasion by pretreated trypomastigotes and promastigotes was also observed. the extracts caused a significant reduction of the multiplicat ...201424548158
isolation of arginase inhibitors from the bioactivity-guided fractionation of byrsonima coccolobifolia leaves and stems.byrsonima coccolobifolia leaf and stem extracts were studied in the search for possible leishmanicidal compounds using arginase (arg) from leishmania amazonensis as a molecular target. flavonoids 1b, 1e-1g, 2a, 2b, and 2d-2f showed significant inhibitory activity, with ic50 values ranging from 0.9 to 4.8 μm. the kinetics of the most active compounds were determined. flavonoids 1e, 1f, 2a, 2b, and 2e were characterized as noncompetitive inhibitors of arg with dissociation constants (ki) ranging f ...201424521209
sod1 plasma level as a biomarker for therapeutic failure in cutaneous leishmaniasis.we show that increased plasma superoxide dismutase 1 (sod1) levels are statistically significant predictors of the failure of pentavalent antimony treatment for cutaneous leishmaniasis caused by leishmania braziliensis. in leishmania amazonensis-infected patients, host sod1 levels can be used to discriminate between localized and drug-resistant diffuse cutaneous leishmaniasis. using in situ transcriptomics (ncounter), we demonstrate a significant positive correlation between host sod1 and interf ...201424511100
the calpain inhibitor mdl28170 induces the expression of apoptotic markers in leishmania amazonensis promastigotes.human cutaneous leishmaniasis is caused by distinct species, including leishmania amazonensis. treatment of cutaneous leishmaniasis is far from satisfactory due to increases in drug resistance and relapses, and toxicity of compounds to the host. as a consequence for this situation, the development of new leishmanicidal drugs and the search of new targets in the parasite biology are important goals.201424498160
leishmania braziliensis and leishmania amazonensis amastigote extracts differ in their enhancement effect on leishmania infection when injected intradermally.it has been reported that repeated intravenous injections of a relatively large amount of leishmania amazonensis amastigote extract (lae) in balb/c mice exacerbates the infection of these mice by leishmania braziliensis. the identification of the extract active principle(s) through physicochemical purification often involves dilution and losses of protein in the course of successive purification procedures. the large amount of the extract required to induce the phenomenon, therefore, hinders the ...201424484604
targeted extracellular signal-regulated kinase activation mediated by leishmania amazonensis requires mp1 scaffold.leishmania amazonensis infection promotes alteration of host cellular signaling and intracellular parasite survival, but specific mechanisms are poorly understood. we previously demonstrated that l. amazonensis infection of dendritic cells (dc) activated extracellular signal-regulated kinase (erk), an map-kinase kinase kinase, leading to altered dc maturation and non-healing cutaneous leishmaniasis. studies using growth factors and cell lines have shown that targeted, robust, intracellular phosp ...201424463270
excreted leishmania peruviana and leishmania amazonensis iron-superoxide dismutase purification: specific antibody detection in colombian patients with cutaneous leishmaniasis.leishmania sp. survival in the vertebrate host depends on the host macrophage immune response as well as on the parasite's defense against free radicals. iron-superoxide dismutase (fe-sod) is a key antioxidant enzyme that contributes to radical superoxide dismutation, preventing the disease from surging and propagating itself. leishmania sp. has various fe-sod isoforms, one of which (fe-sode) is excreted into the medium and, being highly immunogenic, can be considered a very good molecular marke ...201424440468
dynamic identification of h2 epitopes from leishmania (leishmania) amazonensis cysteine proteinase b with potential immune activity during murine infection.peptides from the cooh-terminal extension of cysteine proteinase b from leishmania (leishmania) amazonensis (cyspep) can modulate immune responses in vertebrate hosts. with this hypothesis as base, we used the online analysis tool syfpeithi to predict seven epitopes from this region with potential to bind h2 proteins. we performed proliferation tests and quantified reactive t lymphocytes applying a cytometry analysis, using samples from draining lymph node of lesions from l. (l.) amazonensis-inf ...201424436127
complexes of different nitrogen donor heterocyclic ligands with sbcl3 and phsbcl2 as potential antileishmanial agents against sb(iii)-sensitive and -resistant parasites.novel trivalent antimony complexes with the nitrogen donor heterocyclic ligand 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) have been synthesized by the reaction with sbcl3 or phsbcl2. the crystal structures of [sb(phen)cl3] and [phsb(phen)cl2]ch3cooh were determined and shown to adopt a distorted square pyramid geometry with a five-coordinated sb center. surprisingly, all the complexes, the ligands and phsbcl2 showed very high antileishmanial ac ...201424412095
antileishmanial activity and cytotoxicity of brazilian plants.leishmaniasis is a major public health problem, and the alarming spread of parasite resistance has increased the importance of discovering new therapeutic products. the present study aimed to investigate the in vitro leishmanicidal activity from 16 different brazilian medicinal plants. stationary-phase promastigotes of leishmania amazonensis and murine macrophages were exposed to 44 plant extracts or fractions for 48 h at 37°c, in order to evaluate their antileishmanial activity and cytotoxicity ...201424846006
cross-protective immunity to leishmania amazonensis is mediated by cd4+ and cd8+ epitopes of leishmania donovani nucleoside hydrolase terminal domains.the nucleoside hydrolase (nh) of leishmania donovani (nh36) is a phylogenetic marker of high homology among leishmania parasites. in mice and dog vaccination, nh36 induces a cd4+ t cell-driven protective response against leishmania chagasi infection directed against its c-terminal domain (f3). the c-terminal and n-terminal domain vaccines also decreased the footpad lesion caused by leishmania amazonensis. we studied the basis of the crossed immune response using recombinant generated peptides co ...201424822054
arrabidaea chica hexanic extract induces mitochondrion damage and peptidase inhibition on leishmania spp.currently available leishmaniasis treatments are limited due to severe side effects. arrabidaea chica is a medicinal plant used in brazil against several diseases. in this study, we investigated the effects of 5 fractions obtained from the crude hexanic extract of a. chica against leishmania amazonensis and l. infantum, as well as on the interaction of these parasites with host cells. promastigotes were treated with several concentrations of the fractions obtained from a. chica for determination ...201424818162
antileishmanial activity of the estrogen receptor modulator raloxifene.the treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects. additionally, parasite resistance in the treatment of leishmaniasis has been demonstrated for the majority of drugs available, making the search for more effective and less toxic drugs and treatment regimens a priority for the control of leishmaniasis. the aims of this study were to evaluate the antileishmanial activity of raloxifene in vitro and in vivo and to investigate its mechanism of ...201424810565
in vitro and in vivo antileishmania activity of sesquiterpene lactone-rich dichloromethane fraction obtained from tanacetum parthenium (l.) schultz-bip.the discovery of new treatments for neglected diseases, including leishmaniasis, is a substantial challenge for scientific research. plant extracts have shown potential in the selective treatment of tropical diseases. the present study evaluated the in vitro and in vivo antileishmania effects of a sesquiterpene lactone-rich dichloromethane fraction (df) obtained from the aerial parts of tanacetum parthenium (l.) schultz-bip. in vitro studies of the df indicated an ic50 of 2.40±0.76 μg ml(-1) aga ...201424810433
periodate-oxidized atp modulates macrophage functions during infection with leishmania amazonensis.previously, we showed that treating macrophages with atp impairs the intracellular growth of leishmania amazonensis, and that the p2x7 purinergic receptor is overexpressed during leishmaniasis. in the present study, we directly evaluated the effect of periodate-oxidized atp (oatp) on parasite control in leishmania-infected macrophages. we found that oatp impaired the attachment/entrance of l. amazonensis promastigotes to c57bl/6 mouse macrophages in a p2x7 receptor-independent manner, as macroph ...201424804957
leishmanicidal evaluation of tetrahydroprotoberberine and spirocyclic erythrina-alkaloids.leishmaniasis is one of the world's most problematic diseases in developing countries. traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. in this work, two alkaloids 1 and 2 were obtained from corydalis govaniana wall and seven alkaloids 3-9, were obtained from erythrina verna. the structures of the compounds were confirmed by mass spectrometry and 1d- and 2d-nmr spectroscopy. the leishmanicidal activity of compounds 1-9 a ...201424802983
antileishmanial activity of essential oil from chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in balb/c mice.chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases.201424768411
leishmania amazonensis promastigotes in 3d collagen i culture: an in vitro physiological environment for the study of extracellular matrix and host cell interactions.leishmania amazonensis is the causative agent of american cutaneous leishmaniasis, an important neglected tropical disease. once leishmania amazonensis is inoculated into the human host, promastigotes are exposed to the extracellular matrix (ecm) of the dermis. however, little is known about the interaction between the ecm and leishmania promastigotes. in this study we established l. amazonensis promastigote culture in a three-dimensional (3d) environment mainly composed of collagen i (col i). t ...201424765565
role of protein kinase r in the killing of leishmania major by macrophages in response to neutrophil elastase and tlr4 via tnfα and ifnβ.in cutaneous leishmaniasis, leishmania amazonensis activates macrophage double-stranded, rna-activated protein kinase r (pkr) to promote parasite growth. in our study, leishmania major grew normally in raw cells, raw-expressing dominant-negative pkr (pkr-dn) cells, and macrophages of pkr-knockout mice, revealing that pkr is dispensable for l. major growth in macrophages. pkr activation in infected macrophages with poly i:c resulted in parasite death. fifty percent of l. major-knockout lines for ...201424732131
leukotriene b4 modulates p2x7 receptor-mediated leishmania amazonensis elimination in murine macrophages.atp is an important signaling molecule in the immune system, and it is able to bind the p2x7 purinergic receptor. recently, our group showed that atp-treated macrophages eliminate leishmania amazonensis. it has been reported that leukotriene b4 (ltb4) reduces the parasitic load of infected macrophages. additionally, it has been demonstrated that the p2x7 receptor can induce pla2 activation and arachidonic acid mobilization. based on these findings, we investigated whether ltb4 is produced upon p ...201424729618
antiparasitic activities of novel ruthenium/lapachol complexes.the present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (me-bipy) and 4,4'-methoxybipyridine (meo-bipy)/phosphine/ruthenium(ii) complexes containing lapachol (lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. the [ru(lap)(pph3)2(bipy)]pf6 (1), [ru(lap)(pph3)2(me-bipy)]pf6 (2), [ru(lap)(pph3)2(meo-bipy)]pf6(3) and[ru(lap)(p ...201424727183
purification and biochemical characterization of three myotoxins from bothrops mattogrossensis snake venom with toxicity against leishmania and tumor cells.bothrops mattogrossensis snake is widely distributed throughout eastern south america and is responsible for snakebites in this region. this paper reports the purification and biochemical characterization of three new phospholipases a2 (pla2s), one of which is presumably an enzymatically active asp49 and two are very likely enzymatically inactive lys49 pla2 homologues. the purification was obtained after two chromatographic steps on ion exchange and reverse phase column. the 2d sds-page analysis ...201424724078
in vitro cytokines profile and ultrastructural changes of microglia and macrophages following interaction with leishmania.in the present study, we assessed morphological changes and cytokine production after in vitro interaction with causative agents of american cutaneous leishmaniasis and compared the microglia and macrophage immune responses. cultures of microglia and macrophages infected with stationary-phase promastigotes of leishmania (viannia) shawi, leishmania (viannia) braziliensis or leishmania (leishmania) amazonensis were evaluated 24, 48 and 72 h after interaction. macrophages only presented the classic ...201424717447
in vitro and in vivo efficacy of novel flavonoid dimers against cutaneous leishmaniasis.treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. we previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity against leishmania donovani, the causative agent of visceral leishmaniasis. here, we further investigate their leishmanicidal activities against cutaneous leishmania species. one of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhib ...201424687505
correlation between glucose uptake and membrane potential in leishmania parasites isolated from dcl patients with therapeutic failure: a proof of concept.besides infection with drug-resistant parasites, therapeutic failure in leishmaniasis may be caused by altered drug pharmacokinetics, re-infection, and host immunologic compromise. our aim has been to evaluate if relapses that occur in patients suffering from diffuse cutaneous leishmaniasis (dcl) associate with changes in the fitness of infecting organisms. therefore, in isolates from patients suffering dcl, we correlated glucose uptake and plasma membrane potential and compared the results with ...201424671239
activity of anti-cancer protein kinase inhibitors against leishmania spp.there is an urgent need to develop new and effective treatments for poverty-related neglected diseases. in light of the time required to bring a new drug to market and the cost involved (10-15 years, >1 billion us$), one approach to identifying new treatments for diseases like leishmaniasis is to evaluate drugs that are already registered for the treatment of other diseases. this paper describes the anti-leishmanial activities of 10 fda-approved protein kinase inhibitors already available for th ...201424668412
discovery of the rapanone and suberonone mixture as a motif for leishmanicidal and antifungal applications.leishmaniasis and fungal infections are significant diseases impacting worldwide public health. treatments have developed greatly over time, however, there is a necessity to discover less toxic drugs, which have greater efficacy and are more economically accessible. this work conducted a screening of cerrado species extracts: connarus suberosus planch. (connaraceae), neea theifera oerst. (nyctaginaceae) and myrcia linearifolia cambess. (myrtaceae) against leishmania (leishmania) amazonensis, der ...201424331757
2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites.the 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. all compounds were tested in vitro against four neglected protozoan parasites (giardia intestinalis, trichomonas vaginalis, leishmania amazonensis and trypanosoma cruzi). acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against g. intestinalis and t. vaginalis, showing nanomolar inhibition. compound 13 (ic50=10nm) ...201424529307
salivary gland homogenates from wild-caught sand flies lutzomyia flaviscutellata and lutzomyia (psychodopygus) complexus showed inhibitory effects on leishmania (leishmania) amazonensis and leishmania (viannia) braziliensis infection in balb/c mice.during the natural transmission of leishmania parasites, the infected sand fly female regurgitates promastigotes into the host's skin together with its saliva. it has been reported that vector saliva contains immunomodulatory molecules that facilitate the establishment of infection. thus, the main objective of this study was to evaluate the specificity of lutzomyia (lu.) flaviscutellata and lu. (psychodopygus) complexus salivas on the infectivity of leishmania (l.) (leishmania) amazonensis and l ...201425476864
identification of differentially expressed proteins from leishmania amazonensis associated with the loss of virulence of the parasites.the present study analyzed whether or not the in vitro cultivation for long periods of time of pre-isolated leishmania amazonensis from lesions of chronically infected balb/c mice was able to interfere in the parasites' infectivity using in vivo and in vitro experiments. in addition, the proteins that presented a significant decrease or increase in their protein expression content were identified applying a proteomic approach.201424699271
cell-to-cell transfer of leishmania amazonensis amastigotes is mediated by immunomodulatory lamp-rich parasitophorous extrusions.the last step of leishmania intracellular life cycle is the egress of amastigotes from the host cell and their uptake by adjacent cells. using multidimensional live imaging of long-term-infected macrophage cultures we observed that leishmania amazonensis amastigotes were transferred from cell to cell when the donor host macrophage delivers warning signs of imminent apoptosis. they were extruded from the macrophage within zeiotic structures (membrane blebs, an apoptotic feature) rich in phagolyso ...201424824158
leishmania-mediated inhibition of iron export promotes parasite replication in macrophages.leishmania parasites infect macrophages, cells that play an important role in organismal iron homeostasis. by expressing ferroportin, a membrane protein specialized in iron export, macrophages release iron stored intracellularly into the circulation. iron is essential for the intracellular replication of leishmania, but how the parasites compete with the iron export function of their host cell is unknown. here, we show that infection with leishmania amazonensis inhibits ferroportin expression in ...201424497831
unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents.in this work the synthesis and antiparasitical activity of new 1,5-diaryl-3-oxo-1,4-pentadienyl derivatives are described. first, compounds 1a, 1b, 1c and 1d were prepared by acid-catalyzed aldol reaction between 2-butanone and benzaldehyde, anisaldehyde, p-n,n-dimethylaminobenzaldehyde and p-nitrobenzaldehyde. reacting each of the methyl ketones 1a, 1b, 1c and 1d with the p-substituted benzaldehydes under basic-catalyzed aldol reaction, we further prepared compounds 2a-2p. all twenty compounds ...201424398381
cross-protective effect of a combined l5 plus l3 leishmania major ribosomal protein based vaccine combined with a th1 adjuvant in murine cutaneous and visceral leishmaniasis.two leishmania major ribosomal proteins l3 (lml3) and l5 (lml5) have been described as protective molecules against cutaneous leishmaniasis due to infection with l. major and leishmania braziliensis in balb/c mice when immunized with a th1 adjuvant (non-methylated cpg-oligodeoxynucleotides; cpg-odn). in the present study we analyzed the cross-protective efficacy of an lml3-lml5-cpg odn combined vaccine against infection with leishmania amazonensis and leishmania chagasi (syn. leishmania infantum ...201424382098
constitutive mosaic aneuploidy is a unique genetic feature widespread in the leishmania genus.using fluorescence in situ hybridization, we determined the ploidy of four species of leishmania: leishmania infantum, leishmania donovani, leishmania tropica and leishmania amazonensis. we found that each cell in a strain possesses a combination of mono-, di- and trisomies for all chromosomes; ploidy patterns were different among all strains/species. these results extend those we previously described in leishmania major, demonstrating that mosaic aneuploidy is a genetic feature widespread to th ...201424120456
effectiveness of novel 5-(5-amino-1-aryl-1h-pyrazol-4-yl)-1h-tetrazole derivatives against promastigotes and amastigotes of leishmania amazonensis.in this research, a series of substituted 5-(5-amino-1-aryl-1h-pyrazol-4-yl)-1h-tetrazoles were synthesized and evaluated for in vitro antileishmanial activity. among the derivatives, examined compounds 3b and 3l exhibited promising activity against promastigotes and amastigotes forms of leishmania amazonensis. the cytotoxicity of these compounds was evaluated on murine cells, giving access to the corresponding selectivity index (si).201424119090
neutrophils have a protective role during early stages of leishmania amazonensis infection in balb/c mice.neutrophils are involved in the early stages of immune responses to pathogens. here, we investigated the role of neutrophils during the establishment of leishmania amazonensis infection in balb/c and c57bl/6 mice. first, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. next, we depleted neutrophils prior to infection using rb6-8c5 or 1a8 mab. neutrophil depletion led to faster lesion development, increased paras ...201424102495
fatty acid profiles in leishmania spp. isolates with natural resistance to nitric oxide and trivalent antimony.fatty acids, especially those from phospholipids (plfa), are essential membrane components that are present in relatively constant proportions in biological membranes under natural conditions. however, under harmful growth conditions, such as diseases, environmental changes, and chemical exposure, the fatty acid proportions might vary. if such changes could be identified and revealed to be specific for adverse situations, they could be used as biomarkers. such biomarkers could facilitate the ide ...201424096610
protective effects of the antileishmanial extract of tephrosia cinerea (l.) pers. (fabaceae) against cyclophosphamide-induced damage.tephrosia cinerea l. (pers.) is a tropical species that exhibits antileishmanial activity in leishmania amazonensis promastigote cultures and is commonly used to treat infections, inflammations, ulcers, nervous conditions, and diarrhea. however, no studies have investigated its effects on genetic material. therefore, we evaluated the genotoxic potential, antigenotoxic potential, and cytotoxic effects of hydroalcoholic extracts of t. cinerea leaves. in an in vitro genotoxicity study, human periph ...201425366795
pterocarpanquinone lqb-118 induces apoptosis in leishmania (viannia) braziliensis and controls lesions in infected hamsters.previous results demonstrate that the hybrid synthetic pterocarpanquinone lqb-118 presents antileishmanial activity against leishmania amazonensis in a mouse model. the aim of the present study was to use a hamster model to investigate whether lqb-118 presents antileishmanial activity against leishmania (viannia) braziliensis, which is the major leishmania species related to american tegumentary leishmaniasis. the in vitro antileishmanial activity of lqb-118 on l. braziliensis was tested on the ...201425340550
the comparative genomics and phylogenomics of leishmania amazonensis parasite.leishmaniasis is an infectious disease caused by leishmania species. leishmania amazonensis is a new world leishmania species belonging to the mexicana complex, which is able to cause all types of leishmaniasis infections. the l. amazonensis reference strain mhom/br/1973/m2269 was sequenced identifying 8,802 codifying sequences (cds), most of them of hypothetical function. comparative analysis using six leishmania species showed a core set of 7,016 orthologs. l. amazonensis and leishmania mexica ...201425336895
evidences for leishmanicidal activity of the naphthoquinone derivative epoxy-α-lapachone.in this work, we analyze the leishmanicidal effects of epoxy-α-lapachone on leishmania (viannia) braziliensis and leishmania (leishmania) amazonensis. promasigotes and amastigotes (inhabiting human macrophages) from both species were assayed to verify the compound's activity over the distinct morphological stages. the incubation with epoxy-α-lapachone led to a significant decrease in the numbers of promastigotes from both species in the cultures, in a dose-and time-dependent fashion. the surviva ...201425307687
insulin-like growth factor-i induces arginase activity in leishmania amazonensis amastigote-infected macrophages through a cytokine-independent mechanism.leishmania (leishmania) amazonensis exhibits peculiarities in its interactions with hosts. because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (igf)-i on interactions between l. (l.) amazonensis amastigotes and macrophages. upon stimulation of infected macrophages with igf-i, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. howeve ...201425294956
synthesis and evaluation of the antiparasitic activity of bis-(arylmethylidene) cycloalkanones.a series of bis-(arylmethylidene)-cycloalkanones was synthesized by cross-aldol condensation. the activity of the compounds was evaluated against amastigotes forms of trypanosoma cruzi and promastigotes forms of leishmania amazonensis. the cytotoxicity of the active compounds on uninfected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their antiparasitic effects. six compounds displayed trypanocidal activity against amastigotes intracellular forms of t. cruzi ...201424321832
leishmania amazonensis: characterization of an ecto-pyrophosphatase activity.several ecto-enzymatic activities have been described in the plasma membrane of the protozoan leishmania amazonensis, which is the major etiological agent of diffuse cutaneous leishmaniasis in south america. these enzymes, including ecto-phosphatases, contribute to the survival of the parasite by participating in phosphate metabolism. this work identifies and characterizes the extracellular hydrolysis of inorganic pyrophosphate related to an ecto-pyrophosphatase activity of the promastigote form ...201424316462
a2 and other visceralizing proteins of leishmania: role in pathogenesis and application for vaccine development.visceral leishmaniasis is a re-emergent disease and a significant cause of morbidity worldwide. amongst the more than 20 leishmania species, leishmania donovani, leishmania infantum and more rarely leishmania amazonensis are associated with visceral leishmaniasis. a major question in leishmaniasis research is how these species migrate to and infect visceral organs whereas other species such as leishmania major and leishmania braziliensis remain in the skin, causing tegumentary leishmaniasis. her ...201424264241
brazilian brown propolis elicits antileishmanial effect against promastigote and amastigote forms of leishmania amazonensis.propolis is a complex matrix of chemical constituents extracted from plants and produced by bees which is used in folk medicine due to its several pharmacological properties. its chemical composition varies according to the region where it is produced. this work has studied the antileishmanial activity and cytotoxicity of brown propolis (bp) originating from the semi-arid region of piauí, brazil. the bp showed significant inhibition of the leishmania amazonensis promastigotes growth as well as b ...201424261482
essential oil from chenopodium ambrosioides and main components: activity against leishmania, their mitochondria and other microorganisms.chenopodium ambrosioides is an aromatic herb used by native people to treat parasitic diseases. the aim of this work is to compare the in vitro anti-leishmanial activity of the essential oil (eo) from c. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide) and study their mechanism of action and activity against a panel of microorganism. antileishmanial activity and cytotoxicity of the eo and major components was study. in addition, experiments to elucidate the m ...201424184772
treatment with triterpenic fraction purified from baccharis uncinella leaves inhibits leishmania (leishmania) amazonensis spreading and improves th1 immune response in infected mice.the current medications used to treat leishmaniasis have many side effects for patients; in addition, some cases of the disease are refractory to treatment. therefore, the search for new leishmanicidal compounds is indispensable. recently, it was demonstrated that oleanolic- and ursolic-containing fraction from baccharis uncinella leaves eliminated the promastigote and amastigote forms of leishmania (leishmania) amazonensis and l. (viannia) braziliensis without causing toxic effects for j774 mac ...201424173812
in vitro interaction between paromomycin sulphate and four drugs with leishmanicidal activity against three new world leishmania species.to evaluate in vitro interactions between paromomycin sulphate and the antileishmanial drugs meglumine antimoniate, amphotericin b, miltefosine and azithromycin against intracellular leishmania (leishmania) infantum chagasi, leishmania (viannia) braziliensis and leishmania (leishmania) amazonensis amastigotes in peritoneal mouse macrophages.201423970484
antileishmanial activity of the essential oil from bixa orellana.leishmaniasis is a neglected tropical disease caused by leishmania protozoa. there is currently no vaccine against leishmaniasis, and chemotherapy remains the only effective control. however, conventional drugs are toxic, expensive, and require long periods of treatment, and resistance to clinical chemotherapeutic agents is emerging. recent research on plants has shown a successful approach to obtain new antileishmanial alternatives. herein, the in vitro and in vivo effects of the essential oil ...201423983115
cloning, characterization, and inhibition studies of a β-carbonic anhydrase from leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis.leishmaniasis is an infection provoked by protozoans belonging to the genus leishmania. among the many species and subsepecies of such protozoa, leishmania donovani chagasi causes visceral leishmaniasis. a β-carbonic anhydrase (ca, ec 4.2.1.1) was cloned and characterized from this organism, denominated here ldcca. ldcca possesses effective catalytic activity for the co2 hydration reaction, with kcat of 9.35 × 10(5) s(-1) and kcat/km of 5.9 × 10(7) m(-1) s(-1). a large number of aromatic/heteroc ...201323977960
biochemical and functional characterization of a c-type lectin (bplec) from bothrops pauloensis snake venom.in the present work, we report the isolation and partial biochemical characterization of bplec, a c-type lectin purified from bothrops pauloensis venom by one chromatographic step on an affinity agarose column immobilized with d-galactose. this protein was homogeneous by sds-page under reducing and nonreducing conditions, and was shown to be a 33.6 kda homodimer by maldi tof analysis. bplec presented an isoeletric point of 5.36. its partial sequence of 132 amino acids for each subunit, determine ...201323178369
immunomodulatory activity of ouabain in leishmania leishmania amazonensis-infected swiss mice.ouabain is a cardiotonic steroid identified as an endogenous substance of human plasma, being produced by the adrenal, pituitary, and hypothalamus. despite the studies demonstrating the ability of ouabain to modulate inflammation and other aspects of the immune response, the effects of this substance in leishmaniasis is unknown. the purpose of this work was to understand the immunomodulatory activity of ouabain in experimental leishmaniasis in swiss mice. it was demonstrated that ouabain reduced ...201323052777
in vitro antileishmanial activity of essential oil of vanillosmopsis arborea (asteraceae) baker.the search for new immunopharmacological chemical agents to treat various diseases caused by bacteria, fungi, and protozoa, such as leishmaniasis, for example, has led to the exploration of potential products from plant species and their main active ingredients. antimonial drugs are the current treatment for leishmaniasis. these drugs cause major side effects and frequent discontinuation of treatment. in this study, we evaluated the in vitro leishmanicidal activity of essential oil of vanillosmo ...201323935675
liposomal-lupane system as alternative chemotherapy against cutaneous leishmaniasis: macrophage as target cell.leishmania amazonensis causes human diseases that range from self-healing to diffusion cutaneous lesions. the chemotherapy of leishmaniasis requires long-term treatment and has been based on the use of pentavalent antimonials. liposomes have been used as antileishmanial drug carries and have adjuvant activity in vaccines against several microorganisms, representing an important option to the development of new therapeutics for the disease. in this study, we developed a liposomal formulation cont ...201323933281
leishmanicidal activity of amphotericin b encapsulated in plga-dmsa nanoparticles to treat cutaneous leishmaniasis in c57bl/6 mice.the major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin b (d-amb), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. for this, amb nanoencapsulated in poly(lactic-co-glycolic acid) (plga) and dimercaptosuccinic acid (dmsa) nanoparticles (nano-d-amb) has been developed, and its eff ...201323891944
heme uptake mediated by lhr1 is essential for leishmania amazonensis virulence.the protozoan parasite leishmania amazonensis is a heme auxotroph and must acquire this essential factor from the environment. previous studies showed that l. amazonensis incorporates heme through the transmembrane protein lhr1 (leishmania heme response 1). lhr1-null promastigotes were not viable, suggesting that the transporter is essential for survival. here, we compared the growth, differentiation, and infectivity for macrophages and mice of wild-type, lhr1-single-knockout (lhr1/δlhr1), and l ...201323876801
reactive oxygen species production by quercetin causes the death of leishmania amazonensis intracellular amastigotes.the present study reports the mechanism of the antileishmanial activity of quercetin against the intracellular amastigote form of leishmania amazonensis. treatment with 1 reduced the infection index in l. amazonensis-infected macrophages in a dose-dependent manner, with an ic₅₀ value of 3.4 μm and a selectivity index of 16.8, and additionally increased ros generation also in a dose-dependent manner. quercetin has been described as a pro-oxidant that induces the production of reactive oxygen spec ...201323876028
dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in leishmania (leishmania) amazonensis infection.fisetin, quercetin, luteolin and 7,8-hydroxyflavone show high activity in leishmania cultures and present low toxicity to mammalian cells. in this work, the structural aspects of 13 flavonoids were analyzed for their inhibition of the arginase enzyme from leishmania (leishmania) amazonensis. a higher potency of arginase inhibition was observed with fisetin, which was four and ten times greater than that of quercetin and luteolin, respectively. these data show that the hydroxyl group at position ...201323870955
the eif4e subunits of two distinct trypanosomatid eif4f complexes are subjected to differential post-translational modifications associated to distinct growth phases in culture.the eukaryotic eif4f complex, the cap binding complex, functions during translation initiation through interactions mediated by its three subunits (eif4e, eif4g and eif4a), other initiation factors and the ribosome. in trypanosomatids, various eif4e and eif4g homologues were identified, with two eif4f-like complexes confirmed (eif4e4/eif4g3/eif4ai and eif4e3/eif4g4/eif4ai). here, the expression pattern of these complexes was investigated during leishmania amazonensis and trypanosoma brucei growt ...201323867205
trans- β -caryophyllene: an effective antileishmanial compound found in commercial copaiba oil (copaifera spp.).this study investigated the leishmanicidal activity against leishmania amazonensis of four commercial oils from copaifera spp. named as c1, c2, c3, and c4, the sesquiterpene and diterpene pools obtained from distilling c4, and isolated β -caryophyllene (car). copaiba oils chemical compositions were analyzed by gas chromatography and correlated with biological activities. diterpenes-rich oils c2 and c3 showed antipromastigote activity. sesquiterpenes-rich c1 and c4, and isolated car presented a d ...201323864897
the genome sequence of leishmania (leishmania) amazonensis: functional annotation and extended analysis of gene models.we present the sequencing and annotation of the leishmania (leishmania) amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the amazon region of brazil. l. (l.) amazonensis shares features with leishmania (l.) mexicana but also exhibits unique characteristics regarding geographical distribution and clinical manifestations of cutaneous lesions (e.g. borderline disseminated cutaneous leishmaniasis). predicted genes were scored for orthologous gene families and conserved do ...201323857904
synthesis, antileishmanial activity and structure-activity relationship of 1-n-x-phenyl-3-n'-y-phenyl-benzamidines.two series of n,n'-diphenyl-benzamidines were synthesized as part of a study to search potential new drugs with antileishmanial activity. these compounds were obtained by anilides in pcl5 halogenation reaction with generation in situ of the corresponding benzimidoyl chlorides, and subsequently treatment with adequate anilines. the series i showed expressive results of antileishmanial activity, highlighted the compounds 9a with ic50 = 81.28 μm (log ic50 = 1.91 μm) against leishmania chagasi, 8e w ...201323851118
a novel alkyl phosphocholine-dinitroaniline hybrid molecule exhibits biological activity in vitro against leishmania amazonensis.parasitic protozoa of the leishmania genus cause leishmaniasis, an important complex of tropical diseases that affect about 12 million people around the world. the drugs used to treat leishmaniasis are pentavalent antimonials, miltefosine, amphotericin b and pentamidine. in the present study, we evaluated the effect of a novel alkyl phosphocholine-dinitroaniline hybrid molecule, tc95, against leishmania amazonensis promastigotes and intracellular amastigotes. antiproliferative assays indicated t ...201323845259
the effects of n-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro- β -carboline-3-carboxamide against leishmania amazonensis are mediated by mitochondrial dysfunction.leishmaniasis is a disease that affects millions of people worldwide. the drugs that are available for the treatment of this infection exhibit high toxicity and various side effects. several studies have focused on the development of new chemotherapeutic agents that are less toxic and more effective against trypanosomatids. we investigated the effects of n-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (c4) and its possible targets against l. amazonensis. the result ...201323843887
evaluation of antileishmanial activity of selected brazilian plants and identification of the active principles.this study evaluated extracts, fractions, and isolated compounds from some selected brazilian medicinal plants against strains of promastigotes of leishmania amazonensis and l. brasiliensis in vitro. the cell viability was determined, comparing the results with reference standards. the dichloromethane fractions of the roots, stems, and leaves of allamanda schottii showed ic50 values between 14.0 and 2.0  μ g/ml. plumericin was the main active compound, with ic50 of 0.3 and 0.04  μ g/ml against t ...201323840252
activity of recombinant and natural defensins from vigna unguiculata seeds against leishmania amazonensis.antimicrobial peptides (amps), which are differentiated from other antibiotic peptides, such as gramicidins and polymyxins, because they are synthesized by large enzymatic complex and bear modified amino acids including d-amino acids, are short polymers of l-amino acids synthesized by ribosomes upon which all living organisms rely to defend themselves from invaders or competitor microorganisms. amps have received a great deal of attention from the scientific community as potential new drugs for ...201323816644
activation of leishmania spp. leishporin: evidence that dissociation of an inhibitor not only improves its lipid-binding efficiency but also endows it with the ability to form pores.we have previously shown that various species of leishmania produce a lytic activity, which, in leishmania amazonensis, is mediated by a pore-forming cytolysin, called leishporin. it is toxic for macrophages in vitro and optimally active at ph 5.0 to 5.5 and at 37 °c, suggesting that it might be active inside phagolysosomes. leishporin from both l. amazonensis (a-leishporin) and leishmania guyanensis (g-leishporin) can be activated by proteases, suggesting either a limited proteolysis of an inac ...201323812644
synthesis and antiprotozoal activity of dicationic m-terphenyl and 1,3-dipyridylbenzene derivatives.4,4″-diamidino-m-terphenyl (1) and 36 analogues were prepared and assayed in vitro against t rypanosoma brucei rhodesiense , trypanosoma cruzi , plasmodium falciparum , and leishmania amazonensis . twenty-three compounds were highly active against t. b. rhodesiense or p. falciparum. most noteworthy were amidines 1, 10, and 11 with ic50 of 4 nm against t. b. rhodesiense, and dimethyltetrahydropyrimidinyl analogues 4 and 9 with ic50 values of ≤ 3 nm against p. falciparum. bis-pyridylimidamide deri ...201323795673
reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live leishmania amazonensis amastigotes.after loading with live leishmania (l) amazonensis amastigotes, mouse myeloid dendritic leucocytes/dls are known to undergo reprogramming of their immune functions. in the study reported here, we investigated whether the presence of live l. amazonensis amastigotes in mouse bone marrow-derived dls is able to trigger re-programming of dl lipid, and particularly neutral lipid metabolism.201323785538
cytotoxicity and in vitro antileishmanial activity of antimony (v), bismuth (v), and tin (iv) complexes of lapachol.leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis often associated with drug resistance. lapachol [2-hydroxy-3-(3'-methyl-2-butenyl)-1,4-naphthoquinone] displays a wide range of antimicrobial properties against many pathogens. in this study, using the classic microscopic in vitro model, we have analyzed the effects of a series of lapachol and chlorides complexes with antimony (v), bismuth (v), and tin (iv) against l. amazonensis. all seven compounds exhibit ...201323781165
molluscicidal and leishmanicidal activity of the leaf essential oil of syzygium cumini (l.) skeels from brazil.the chemical composition and biological potential of the essential oil extracted from syzygium cumini leaves collected in brazil were examined. gc/ms analyses revealed a high abundance of monoterpenes (87.12%) in the oil. eleven compounds were identified, with the major components being α-pinene (31.85%), (z)-β-ocimene (28.98%), and (e)-β-ocimene (11.71%). to evaluate the molluscicidal effect of the oil, it was tested against biomphalaria glabrata and the lc₅₀ obtained was 90 mg/l. the essential ...201323776029
effects of a marine serine protease inhibitor on viability and morphology of trypanosoma cruzi, the agent of chagas disease.it has been reported that serine peptidase activities of trypanosoma cruzi play crucial roles in parasite dissemination and host cell invasion and therefore their inhibition could affect the progress of chagas disease. the present study investigates the interference of the stichodactyla helianthus kunitz-type serine protease inhibitor (shpi-i), a 55-amino acid peptide, in t. cruzi serine peptidase activities, parasite viability, and parasite morphology. the effect of this peptide was also studie ...201323770204
inflammasome-derived il-1β production induces nitric oxide-mediated resistance to leishmania.parasites of the leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. these parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (no). in this study we show that the nlrp3 inflammasome is activated in response to leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as ...201323749230
in vitro evaluation of 4-phenyl-5-(4'-x-phenyl)-1,3,4-thiadiazolium-2-phenylaminide chlorides and 3[n-4'-x-phenyl]-1,2,3-oxadiazolium-5-olate derivatives on nitric oxide synthase and arginase activities of leishmania amazonensis.leishmaniasis is a spectrum of infectious diseases caused by leishmania protozoan parasites. the purpose of this study was to perform, in vitro, a comparative analysis of the activity amastigotes. results showed excellent efficacy of all compounds against axenic amastigotes, compared to pentamidine isethionate, the reference drug used. the cytotoxic effect of these mesoionic compounds of six mesoionic compounds (three 1,3,4-thiadiazolium-2-aminide and three 1,2,3-oxadiazolium-5-olate class compo ...201323693031
an antigenic domain of the leishmania amazonensis nucleoside triphosphate diphosphohydrolase (ntpdase 1) is associated with disease progression in susceptible infected mice.an antigenic conserved b domain was previously identified within nucleoside triphosphate diphosphohydrolases (ntpdases) of plants and parasites. now, the r-potdomain b, a 6× his-tag polypeptide belonging to the conserved b domain from the potato apyrase, and synthetic peptides lbb1lj and lbb2lj derived from the b domain from leishmania ntpdase 1 were used as molecular tools for studies of the leishmania amazonensis ntpdase 1. widespread subcellular location of the specific ntpdase 1 was detected ...201323681191
in vitro and in vivo antileishmanial and trypanocidal studies of new n-benzene- and n-naphthalenesulfonamide derivatives.we report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of n-substituted benzene and naphthalenesulfonamides 1-15. compounds 1-15 were screened in vitro against leishmania infantum , leishmania braziliensis , leishmania guyanensis , leishmania amazonensis , and trypanosoma cruzi . sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward t. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia i ...201324151871
synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against leishmania spp.a new series of 5-(1-aryl-3-methyl-1h-pyrazol-4-yl)-1h-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1h-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against leishmania braziliensis and leishmania amazonensis promastigotes in vitro. in parallel, the cytotoxicity of these compounds was evaluated on the raw 264.7 cell line. the results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (ic50/24h=15±0.14 μm) and 3,4-di ...201324125880
inhibition of leishmania (leishmania) amazonensis and rat arginases by green tea egcg, (+)-catechin and (-)-epicatechin: a comparative structural analysis of enzyme-inhibitor interactions.epigallocatechin-3-gallate (egcg), a dietary polyphenol (flavanol) from green tea, possesses leishmanicidal and antitrypanosomal activity. mitochondrial damage was observed in leishmania treated with egcg, and it contributed to the lethal effect. however, the molecular target has not been defined. in this study, egcg, (+)-catechin and (-)-epicatechin were tested against recombinant arginase from leishmania amazonensis (arg-l) and rat liver arginase (arg-1). the compounds inhibit arg-l and arg-1 ...201324260115
genotoxicity and antileishmanial activity evaluation of physalis angulata concentrated ethanolic extract.antileishmanial in vitro tests, as well as ames and micronucleus assays were performed with a concentrated ethanolic extract of physalis angulata (eepa) results: eepa did not present mutagenic effect in salmonella typhimurium strains at concentration reaching 3000 μg/plate and did not induce mutagenic effects after two oral administrations with a 24h interval at a dose level of 2000 mg/kg. eepa presented antileishmanial activity and presented an ic₅₀ value of 5.35 ± 2.50 μg/ml and 4.50 ± 1.17 μg ...201324231691
synthetic oxoisoaporphine alkaloids: in vitro, in vivo and in silico assessment of antileishmanial activities.leishmaniasis is a growing health problem worldwide. as there are certain drawbacks with the drugs currently used to treat human leishmaniasis and resistance to these drugs is emerging, there is a need to develop novel antileishmanial compounds, among which isoquinoline alkaloids are promising candidates. in this study, 18 novel oxoisoaporphine derivatives were synthesized and their possible antileishmanial activity was evaluated. the in vitro activity of these derivatives against leishmania ama ...201324204870
strychnos pseudoquina and its purified compounds present an effective in vitro antileishmanial activity.the development of new and cost-effective alternative therapeutic strategies to treat leishmaniasis has become a high priority. in the present study, the antileishmanial activity of strychnos pseudoquina st. hil. was investigated and pure compounds that presented this biological effect were isolated. an ethyl acetate extract was prepared, and it proved to be effective against leishmania amazonensis. a bioactivity-guided fractionation was performed, and two flavonoids were identified, quercetin 3 ...201324194781
in vitro antiparasitic activity and chemical composition of the essential oil obtained from the fruits of piper cubeba.protozoans of the trypanosomatid family cause the neglected tropical diseases leishmaniasis and trypanosomiasis, for which few drugs are available. in this context our group has recently reported that the essential oil obtained by steam distillation of the fruits of piper cubeba is active against schistosoma mansoni. therefore, we have investigated the in vitro effects of the essential oil against the trypomastigote and amastigote forms of trypanosoma cruzi isolated from an llcmk₂ cell line cult ...201324288276
leishmania amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation during cell cycle.here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of leishmania (l.) amazonensis promastigotes, the main causative agent of tegumentary leishmaniasis in the americas. we show evidences that during the cell cycle, l. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. we used dapi-staining and edu-la ...201324278433
in vitro cytocidal effects of the essential oil from croton cajucara (red sacaca) and its major constituent 7- hydroxycalamenene against leishmania chagasi.visceral leishmaniasis is the most serious form of leishmaniasis and can be lethal if left untreated. currently available treatments for these parasitic diseases are frequently associated to severe side effects. the leaves of croton cajucara are used as an infusion in popular medicine to combat several diseases. previous studies have demonstrated that the linalool-rich essential oil from c. cajucara (white sacaca) is extremely efficient against the tegumentary specie leishmania amazonensis. in t ...201324088644
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