| in vitro and in vivo effects of (-)-epigallocatechin 3-o-gallate on leishmania amazonensis. | (-)-epigallocatechin 3-o-gallate (1), the most abundant flavanol in green tea, has been reported to have antiproliferative effects on trypanosoma cruzi. the present study reports the effects in vitro and in vivo of 1 on leishmania amazonensis. l. amazonensis-infected macrophages treated with 1 exhibited a significant reduction of the infection index in a dose-dependent manner, with an ic50 value of 1.6 μm. oral administration of 1 on l. amazonensis-infected balb/c mice (30 mg/kg/day) resulted in ... | 2013 | 24106750 |
| 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 ... | 2014 | 24102495 |
| 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 ... | 2014 | 24096610 |
| 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 ... | 2013 | 24088644 |
| assembly of the leishmania amazonensis flagellum during cell differentiation. | the flagellar cytoskeleton of leishmania promastigotes contains the canonical 9+2 microtubular axoneme and a filamentous structure, the paraflagellar rod (pfr), which is present alongside the axoneme. in contrast to promastigotes, which contain a long and motile flagellum, the amastigote form of leishmania displays a short flagellum without a pfr that is limited to the flagellar pocket domain. here, we investigated the biogenesis of the leishmania flagellum at 0, 4, 6 and 24h of differentiation. ... | 2013 | 24041804 |
| 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 ... | 2014 | 23983115 |
| 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 ... | 2013 | 23977960 |
| 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. | 2014 | 23970484 |
| 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 ... | 2013 | 23935675 |
| 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 ... | 2013 | 23933281 |
| 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 ... | 2013 | 23891944 |
| 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 ... | 2013 | 23876801 |
| 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 ... | 2013 | 23876028 |
| 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 ... | 2013 | 23870955 |
| 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 ... | 2013 | 23867205 |
| 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 ... | 2013 | 23864897 |
| 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 ... | 2013 | 23857904 |
| 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 ... | 2013 | 23851118 |
| 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 ... | 2013 | 23845259 |
| 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 ... | 2013 | 23843887 |
| 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 ... | 2013 | 23840252 |
| 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 ... | 2013 | 23816644 |
| 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 ... | 2013 | 23812644 |
| 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 ... | 2013 | 23795673 |
| 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. | 2013 | 23785538 |
| 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 ... | 2013 | 23781165 |
| 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 ... | 2013 | 23776029 |
| 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 ... | 2013 | 23770204 |
| 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 ... | 2013 | 23749230 |
| 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 ... | 2013 | 23693031 |
| 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 ... | 2013 | 23681191 |
| proteomic analysis reveals differentially expressed proteins in macrophages infected with leishmania amazonensis or leishmania major. | cba macrophages effectively control leishmania major infection, yet are permissive to leishmania amazonensis. employing a transcriptomic approach, we previously showed the up-regulation of the genes involved in the classical pathway of macrophage activation in resistant mice. however, microarray analyses do not evaluate changes in gene expression that occur after translation. to circumvent this analytical limitation, we employed a proteomics approach to increase our understanding of the modulati ... | 2016 | 23628411 |
| synthesis and biological evaluation against leishmania amazonensis of a series of alkyl-substituted benzophenones. | nine o-alkyl and o-prenyl derivatives were synthesized from commercial 2,4-dihydroxybenzophenone, 4,e4,4'-dihydroxybenzophenone and were evaluated for their leishmanicidal activity against promastigote forms of leishmania amazonensis, as well their toxicity in murine macrophages. all derivatives exhibited better biological activity than their hydroxylated benzophenones precursors, and new compound lfqm-123 (3c) was 250-fold more active than its precursor 4,4'-dihydroxybenzophenone (3). moreover, ... | 2013 | 23623672 |
| the role of surface glycoconjugates in leishmania midgut attachment examined by competitive binding assays and experimental development in sand flies. | binding of promastigotes to the sand fly midgut epithelium is regarded as an essential part of the leishmania life cycle in the vector. among leishmania surface molecules putatively involved in attachment to the sand fly midgut, two gpi-anchored molecules are the most prominent: lipophosphoglycan (lpg) and promastigote surface protease gp63. in this work, we examined midgut attachment of leishmania lines mutated in gpi-anchored molecules and compared results from 2 different techniques: in vivo ... | 2013 | 23611086 |
| new amide derivatives of quinoxaline 1,4-di-n-oxide with leishmanicidal and antiplasmodial activities. | malaria and leishmaniasis are two of the world's most important tropical parasitic diseases. continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-n-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against plasmodium falciparum fcr-3 strain, leishmania infantum and leishmania amazonensis. their toxicity against vero cells (normal monkey kidney cells) was also asses ... | 2013 | 23609622 |
| high content analysis of primary macrophages hosting proliferating leishmania amastigotes: application to anti-leishmanial drug discovery. | human leishmaniases are parasitic diseases causing severe morbidity and mortality. no vaccine is available and numerous factors limit the use of current therapies. there is thus an urgent need for innovative initiatives to identify new chemotypes displaying selective activity against intracellular leishmania amastigotes that develop and proliferate inside macrophages, thereby causing the pathology of leishmaniasis. | 2013 | 23593521 |
| drimanes from drimys brasiliensis with leishmanicidal and antimalarial activity. | this paper evaluates chcl3 and ch3oh extracts of the stem bark, branches and leaves of drimys brasiliensis and drimane sesquiterpenes isolated from the stem bark against strains of leishmania amazonensis and leishmania braziliensis promastigotes and plasmodium falciparum trophozoites. all of the extracts and compounds were tested in cell lines in comparison with reference standards and cell viability was determined by the xtt method. the chcl3 and ch3oh extracts from the stem bark and branches y ... | 2013 | 23579790 |
| in vitro leishmanicidal and cytotoxic activities of the glycoalkaloids from solanum lycocarpum (solanaceae) fruits. | leishmaniasis is an infection caused by a protozoan parasite of the genus leishmania and is the second most prevalent parasitic protozoal disease after malaria in the world. we report the in vitro leishmanicidal activity on promastigote forms of leishmania amazonensis and cytotoxicity, using llcmk2 cells, of the glycoalkaloids from the fruits of solanum lycocarpum, determined by colorimetric methods. the alkaloidic extract was obtained by acid-base extraction; solamargine and solasonine were iso ... | 2013 | 23576350 |
| eupomatenoid-5 isolated from leaves of piper regnellii induces apoptosis in leishmania amazonensis. | leishmania spp. are protozoa responsible for leishmaniasis, a neglected disease that kills up to 50,000 people every year. current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy and safety and increased drug resistance. an urgent need exists to find new and more affordable drugs. our previous study demonstrated the antileishmanial activity of eupomatenoid-5, a neolignan obtained from leaves of piper regnellii var. pallescens. the aim of the present s ... | 2013 | 23573160 |
| activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis. | the currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the leishmania parasites. here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against leishmania amazonensis. mefloquine was effective against promastigotes in axenic cultures and showed an ic50 (concentration giving half-maximal inhibition) value of 8.4±0.7 µm. in addition, mefloquine, chloroquine and hyd ... | 2013 | 23538561 |
| potent naphthoquinones against antimony-sensitive and -resistant leishmania parasites: synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition. | continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. these and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of leishmania infantum (syn. leishmania chagasi) and leishmania amazonensis. the toxicity of these compounds to mammalian cells ... | 2013 | 23535320 |
| eugenia uniflora l. essential oil as a potential anti-leishmania agent: effects on leishmania amazonensis and possible mechanisms of action. | eugenia uniflora l. is a member of the myrtaceae family and is commonly known as brazilian cherry tree. in this study, we evaluated the chemical composition of eugenia uniflora l. essential oil (eueo) by using gas chromatography-mass spectrometry (gc-ms) and assessed its anti-leishmania activity. we also explored the potential mechanisms of action and cytotoxicity of eueo. thirty-two compounds were identified, which constituted 92.65% of the total oil composition. the most abundant components we ... | 2013 | 23533469 |
| parasite burden in leishmania (leishmania) amazonensis-infected mice: validation of luciferase as a quantitative tool. | given the lack of effective and safe alternatives to the drugs already in use, considerable efforts are being applied to the search of new therapeutic options to treat leishmaniasis. a necessary step in the discovery of antileishmanial drugs is the validation of drug candidates in mouse models. the standard methods to quantify the parasite burden in animal models, mainly culture-based, are time consuming and expensive. in recent years, in vivo imaging systems have been proposed as a tool to over ... | 2013 | 23466934 |
| antileishmanial activity of 5-methyl-2,2' : 5',2″-terthiophene isolated from porophyllum ruderale is related to mitochondrial dysfunction in leishmania amazonensis. | recently, our group isolated and reported the antiproliferative activity in promastigotes and axenic amastigote forms of leishmania amazonensis treated with 5-methyl-2,2':5',2″-terthiophene (compound a) and 5'-methyl-[5-(4-acetoxy-1-butynyl)]-2,2'-bi-thiophene (compound b) isolated from the aerial parts of porophyllum ruderale. here, we demonstrated that both compounds exhibited activity against intracellular amastigotes showing ic50 values of 37 and 51 µg/ml for compounds a and b, respectively. ... | 2013 | 23457021 |
| leishmanicidal activity of cecropia pachystachya flavonoids: arginase inhibition and altered mitochondrial dna arrangement. | the plant cecropia pachystachya trécul is widely used in brazilian ethnomedicine to treat hypertension, asthma, and diabetes. arginase is an enzyme with levels that are elevated in these disorders, and it is central to leishmania polyamine biosynthesis. the aims of this study were to evaluate antileishmanial activity and inhibition of the arginase enzyme by c. pachystachya extracts, and to study changes in cellular organization using electron microscopy. the ethanol extract of c. pachystachya wa ... | 2013 | 23453911 |
| bnsp-7 toxin, a basic phospholipase a2 from bothrops pauloensis snake venom, interferes with proliferation, ultrastructure and infectivity of leishmania (leishmania) amazonensis. | this paper reports the effects of bnsp-7 toxin, a catalytically inactive phospholipase a2 from bothrops pauloensis snake venom, on leishmania (leishmania) amazonensis. bnsp-7 presented activity against promastigote parasite forms both in the mtt assay, with ic50 of 58.7 μg ml(-1) of toxin, and a growth curve, inhibiting parasite proliferation 60-70% at concentrations of 50-200 μg ml(-1) of toxin 96 h after treatment. also, the toxin presented effects on amastigotes, reducing parasite viability b ... | 2013 | 23442579 |
| antileishmanial activity of diterpene acids in copaiba oil. | leishmaniasis is a neglected tropical disease. according to the world health organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. the goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against leishmania amazonensis. meth ... | 2013 | 23440116 |
| cluster randomised trial to evaluate the effectiveness of a vaccine against cutaneous leishmaniasis in the caratinga microregion, south-east brazil. | the eco-epidemiological complexity of american cutaneous leishmaniasis (acl) has made it difficult to devise an efficient strategy for management of the disease, and development of an effective vaccine remains the most promising approach. the objective of the study was to determine the reduction in incidence of acl following intramuscular administration of two doses of a killed leishmania (leishmania) amazonensis vaccine. | 2013 | 23423433 |
| the natural absence of rpa1n domain did not impair leishmania amazonensis rpa-1 participation in dna damage response and telomere protection. | we have previously shown that the subunit 1 of leishmania amazonensis rpa (larpa-1) alone binds the g-rich telomeric strand and is structurally different from other rpa-1. it is analogous to telomere end-binding proteins described in model eukaryotes whose homologues were not identified in the protozoan´s genome. here we show that larpa-1 is involved with damage response and telomere protection although it lacks the rpa1n domain involved with the binding with multiple checkpoint proteins. we ind ... | 2013 | 23388105 |
| iron uptake controls the generation of leishmania infective forms through regulation of ros levels. | during its life cycle, leishmania undergoes extreme environmental changes, alternating between insect vectors and vertebrate hosts. elevated temperature and decreased ph, conditions encountered after macrophage invasion, can induce axenic differentiation of avirulent promastigotes into virulent amastigotes. here we show that iron uptake is a major trigger for the differentiation of leishmania amazonensis amastigotes, independently of temperature and ph changes. we found that iron depletion from ... | 2013 | 23382545 |
| triphenylmethane derivatives have high in vitro and in vivo activity against the main causative agents of cutaneous leishmaniasis. | the current standard of care for cutaneous leishmaniasis (cl) is organic antimonial compounds, but the administration of these compounds is complicated by a low therapeutic - toxic index, as well as parenteral administration. thus, there is an urgent need for the development of new and inexpensive therapies for the treatment of cl. in this study, we evaluate the activity of the triphenylmethane (tpm) class of compounds against three species of leishmania which are pathogenic in humans. the tpm h ... | 2013 | 23341885 |
| antiprotozoal activity of quinonemethide triterpenes from maytenus ilicifolia (celastraceae). | the present study describes the leishmanicidal and trypanocidal activities of two quinonemethide triterpenes, maytenin (1) and pristimerin (2), isolated from maytenus ilicifolia root barks (celastraceae). the compounds were effective against the trypanosomatidae leishmania amazonensis and leishmania chagasi and trypanosoma cruzi, etiologic agents of leishmaniasis and chagas' disease, respectively. the quinonemethide triterpenes 1 and 2 exhibited a marked in vitro leishmanicidal activity against ... | 2013 | 23322069 |
| an alternative in vitro drug screening test using leishmania amazonensis transfected with red fluorescent protein. | fluorescent and colorimetric reporter genes are valuable tools for drug screening models, since microscopy is labor intensive and subject to observer variation. in this work, we propose a fluorimetric method for drug screening using red fluorescent parasites. fluorescent leishmania amazonensis were developed after transfection with integration plasmids containing either red (rfp) or green fluorescent protein (gfp) genes. after transfection, wild-type (lawt) and transfected (lagfp and larfp) para ... | 2013 | 23312610 |
| different secreted phosphatase activities in leishmania amazonensis. | leishmania has strong acid phosphatase activity on the external surface of the plasma membrane and secreted into the extracellular milieu. secreted acid phosphatase (sacp), which is the most abundant secreted protein of leishmania, is also a virulence factor that plays a role in vertebrate infection and survival in sand flies. in this study, we characterized the secreted phosphatase activities in leishmania amazonensis. both acidic and alkaline secreted phosphatase activities were observed with ... | 2013 | 23305417 |
| lqb-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in leishmania amazonensis. | the pterocarpanquinone lqb-118, previously demonstrated to be effective in vivo via oral delivery, was investigated for its mechanism in selective parasite killing. | 2013 | 23288404 |
| the histopathological and immunological pattern of cba mice infected with leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives. | because there is no vaccine in clinical use, control of leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with leishmania amazonensis. in this study, c ... | 2013 | 23219949 |
| hybrid furoxanyl n-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates. | neglected diseases represent a major health problem. it is estimated that one third of the world population is infected with tuberculosis and additionally leishmaniosis and chagas disease affect approximately 30 million people. n-acylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases. on the other hand, furoxan system has been studied as pharmacophore for leishmaniosis and chagas diseases. here we report on the design an ... | 2013 | 23202852 |
| ocular experimental leishmaniasis in c57bl/10 and balb/c mice induced by leishmania amazonensis infection. | there are few studies on human ocular leishmaniasis found in the literature. the purpose of this study was to describe experimental ocular leishmaniasis, caused by leishmania amazonensis evaluating two different infection routes: intravitreal and instillation in c57bl/10 and balb/c mice. in this work all animals presented low anti-leishmania igm and igg titers regardless of the infection route or mouse strain. the histopathological eye analysis showed that the mice inoculated by the intravitreal ... | 2013 | 23201219 |
| leishmanicidal, antiproteolytic and antioxidant evaluation of natural biflavonoids isolated from garcinia brasiliensis and their semisynthetic derivatives. | the natural biflavonoids morelloflavone-4‴-o-β-d-glycosyl (1), (±)-fukugiside (2) and morelloflavone (3) were isolated from the ethyl acetate extract (eaee) of dried and powdered fruit epicarps of garcinia brasiliensis and derivatives of morelloflavone were semi-synthesised. morelloflavone-7,4',7″,3‴,4‴-penta-o-acetyl (4), morelloflavone-7,4',7″,3‴,4‴-penta-o-methyl (5) and morelloflavone-7,4',7″,3‴,4‴-penta-o-butanoyl (6) were prepared by acylation and alkylation reactions. all compounds showed ... | 2012 | 23178961 |
| 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 ... | 2013 | 23178369 |
| phosphatidylserine exposure on the surface of leishmania amazonensis amastigotes modulates in vivo infection and dendritic cell function. | leishmania amazonensis parasites can cause diverse forms of leishmaniasis in humans and persistent lesions in most inbred strains of mice. in both cases, the infection is characterized by a marked immunosuppression of the host. we previously showed that amastigote forms of the parasite make use of surface-exposed phosphatidylserine (ps) molecules to infect host cells and promote alternative macrophage activation, leading to uncontrolled intracellular proliferation of the parasites. in this study ... | 2016 | 23163958 |
| 17-aag kills intracellular leishmania amazonensis while reducing inflammatory responses in infected macrophages. | leishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. second-line drugs are less efficacious, cause a range of side effects and can be costly. the formulation of new generations of drugs, especially in developing countries, has become mandatory. | 2012 | 23152914 |
| synthesis, antitumor, antitrypanosomal and antileishmanial activities of benzo[4,5]canthin-6-ones bearing the n'-(substituted benzylidene)-carbohydrazide and n-alkylcarboxamide groups at c-2. | a series of novel benzo[4,5]canthin-6-ones, bearing the n'-(substituted benzylidene)-carbohydrazide (11a-e) and n-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against trypanosoma cruzi and leishmania amazonensis. the results indicated that n-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor act ... | 2012 | 23124560 |
| 4-(1h-pyrazol-1-yl) benzenesulfonamide derivatives: identifying new active antileishmanial structures for use against a neglected disease. | leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. in this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1h-pyrazol-1-yl)benzenesulfonamides. our experimental data showed an active profile for some compounds against leishmania infantum and leishmania amaz ... | 2012 | 23117435 |
| improved antileishmanial activity of dppz through complexation with antimony(iii) and bismuth(iii): investigation of the role of the metal. | two novel trivalent antimony(iii) and bismuth(iii) complexes with the nitrogen-donor heterocyclic ligand dipyrido[3,2-a:2',3'-c]phenazine (dppz) were synthesized and characterized as [sb(dppz)cl₃]∙h₂o∙ch₃oh and [bi(dppz)cl₃]. the crystal structure of sb(iii) complex was determined by x-ray crystallography. these complexes were evaluated for their activity against the promastigote form of sb(iii)-sensitive and -resistant leishmania infantum chagasi and leishmania amazonensis strains. both complex ... | 2012 | 23099618 |
| the cytotoxic and antileishmanial activity of extracts and fractions of leaves and fruits of azadirachta indica (a juss.). | the leishmaniases are severe parasitic diseases that occur worldwide, caused by protozoa of the genus leishmania. studies with medicinal plants can lead to a range of possibilities for treating and improving the patients' quality of life. research on azadirachta indica fractions and extracts has shown that they have excellent anti-leishmanial activity based on bioactivity-guided fractionation of ethanolic extracts of leaves and seeds and in vitro activity against promastigotes. in this research ... | 2012 | 23096354 |
| cristaxenicin a, an antiprotozoal xenicane diterpenoid from the deep sea gorgonian acanthoprimnoa cristata. | a new xenicane diterpenoid, cristaxenicin a (1), has been isolated from the deep sea gorgonian acanthoprimnoa cristata. the structure of 1 was elucidated on the basis of spectral analysis including nmr and ms. the absolute configuration of 1 was determined on the basis of quantum chemical calculation of cd spectra. cristaxenicin a (1) showed antiprotozoal activities against leishmania amazonensis and trypanosoma congolense with ic(50) values of 0.088 and 0.25 μm, respectively. | 2012 | 23057655 |
| immunopathogenesis of non-healing american cutaneous leishmaniasis and progressive visceral leishmaniasis. | the outcomes of leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. while subclinical infection and self-healing cutaneous leishmaniasis (cl) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (vl). it is known that infection control requires th1-differentiation cytokines (il-12, il-18, and il-27) and th1 cell and macrophage activation. however, there is no gen ... | 2012 | 23053396 |
| 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 ... | 2013 | 23052777 |
| dillapiole as antileishmanial agent: discovery, cytotoxic activity and preliminary sar studies of dillapiole analogues. | in this paper, the isolation of dillapiole (1) from piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structure-activity relationships (sar). compounds were evaluated for in vitro antileishmanial activity and cytoto ... | 2012 | 22996811 |
| dolabelladienetriol, a compound from dictyota pfaffii algae, inhibits the infection by leishmania amazonensis. | chemotherapy for leishmaniasis, a disease caused by leishmania parasites, is expensive and causes side effects. furthermore, parasite resistance constitutes an increasing problem, and new drugs against this disease are needed. in this study, we examine the effect of the compound 8,10,18-trihydroxy-2,6-dolabelladiene (dolabelladienetriol), on leishmania growth in macrophages. the ability of this compound to modulate macrophage function is also described. | 2012 | 22970332 |
| intramuscular and topical treatment of cutaneous leishmaniasis lesions in mice infected with leishmania amazonensis using coumarin (-) mammea a/bb. | treatment of cutaneous leishmaniasis remains limited to a few available options. recent studies showed in vitro antileishmanial activity of (-) mammea a/bb, a coumarin isolated from leaves of calophyllum brasiliense. moreover, the dichloromethane crude extract and hexane fraction from this plant demonstrated in vivo activity in mice infected with leishmania amazonensis. we evaluated the antileishmanial activity of (-) mammea a/bb in the l. amazonensis balb/c mice model. the animals were given in ... | 2012 | 22954418 |
| in vivo and in vitro leishmania amazonensis infection induces autophagy in macrophages. | autophagy is the primary mechanism of degradation of cellular proteins and at least two functions can be attributed to this biological phenomenon: increased nutrient supply via recycling of the products of autophagy under nutrient starvation; and antimicrobial response involved in the innate immune system. many microorganisms induce host cell autophagy and it has been proposed as a pathway by which parasites compete with the host cell for limited resources. in this report we provide evidence tha ... | 2012 | 22939777 |
| targeting host syntaxin-5 preferentially blocks leishmania parasitophorous vacuole development in infected cells and limits experimental leishmania infections. | our previous observations established a role for syntaxin-5 in the development of leishmania parasitophorous vacuoles (lpvs). in this study, we took advantage of the recent identification of retro-2, a small organic molecule that can cause the redistribution of syntaxin-5; we show herein that retro-2 blocks lpv development within 2 hours of adding it to cells infected with leishmania amazonensis. in infected cells incubated for 48 hours with retro-2, lpv development was significantly limited; fu ... | 2012 | 22885104 |
| effect of 3-alkylpyridine marine alkaloid analogues in leishmania species related to american cutaneous leishmaniasis. | a series of oxygenated analogues of marine 3-alkylpyridine alkaloids were synthesized, and their leishmanicidal activity was assayed. all compounds were prepared from 3-pyridinepropanol in few steps and in good yields. the key step for the synthesis of these compounds was a classic williamson etherification under phase-transfer conditions. besides toxicity in peritoneal macrophages, the compounds exhibited a significant leishmanicidal activity. of twelve compounds tested, five showed a strong le ... | 2012 | 22882996 |
| benzaldehyde thiosemicarbazone derived from limonene complexed with copper induced mitochondrial dysfunction in leishmania amazonensis. | leishmaniasis is a major health problem that affects more than 12 million people. treatment presents several problems, including high toxicity and many adverse effects, leading to the discontinuation of treatment and emergence of resistant strains. | 2012 | 22870222 |
| synthesis, dna binding and antileishmanial activity of low molecular weight bis-arylimidamides. | the effects of reducing the molecular weight of the antileishmanial compound db766 on dna binding affinity, antileishmanial activity and cytotoxicity are reported. the bis-arylimidamides were prepared by the coupling of aryl s-(2-naphthylmethyl)thioimidates with the corresponding amines. specifically, we have prepared new series of bis-arylimidamides which include 3a, 3b, 6, 9a, 9b, 9c, 13, and 18. three compounds 9a, 9c, and 18 bind to dna with similar or moderately lower affinity to that of db ... | 2012 | 22840696 |
| cutaneous leishmaniasis in northeastern brazil: a critical appraisal of studies conducted in state of pernambuco. | american cutaneous leishmaniasis (acl) is a complex disease with clinical and epidemiological features that may vary from region to region. in fact, at least seven different leishmania species, including leishmania (viannia) braziliensis, leishmania (viannia) guyanensis, leishmania (viannia) lainsoni, leishmania (viannia) naiffi, leishmania (viannia) shawi, leishmania (viannia) lindenbergi, and leishmania (leishmania) amazonensis, have been implicated in the etiology of acl in brazil, and numero ... | 2012 | 22836662 |
| leishmania amazonensis fails to induce the release of reactive oxygen intermediates by cba macrophages. | cba mouse macrophages effectively control leishmania major infection, yet are permissive to leishmania amazonensis. it has been established that some leishmania species are destroyed by reactive oxygen species (ros). however, other species of leishmania exhibit resistance to ros or even down-modulate ros production. we hypothesized that l. amazonensis-infected macrophages reduce ros production soon after parasite-cell interaction. employing a highly sensitive analysis technique based on chemilum ... | 2012 | 22817661 |
| heme uptake by leishmania amazonensis is mediated by the transmembrane protein lhr1. | trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. however, the molecular pathway responsible for heme acquisition by these organisms is unknown. here we show that l. amazonensis lhr1, a homolog of the c. elegans plasma membrane heme transporter hrg-4, functions in heme transport. tagged lhr1 localized to the plasma membrane and to endocytic compartments, in both l. amazonensis and mammalian cells. heme deprivatio ... | 2012 | 22807677 |
| therapeutic efficacy induced by the oral administration of agaricus blazei murill against leishmania amazonensis. | the development of therapeutic alternatives to treat leishmaniasis has received considerable attention. the present study aimed to investigate the efficacy of the agaricus blazei murill water extract (abm) to treat balb/c mice infected with leishmania amazonensis. first, a dose-titration curve was performed. the most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). i ... | 2012 | 22797606 |
| investigation of biological activities of dichloromethane and ethyl acetate fractions of platonia insignis mart. seed. | platonia insignis mart., a native species of the brazilian amazon more commonly known as bacuri, is a member of the clusiaceae family. in this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from p. insignis seed ethanolic extract using different experimental models. our results demonstrate in vitro antioxidant effects, by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1,1-dip ... | 2013 | 22788872 |
| mitochondrial damage contribute to epigallocatechin-3-gallate induced death in leishmania amazonensis. | epigallocatechin-3-gallate (egcg), the most abundant flavonoid in green tea, has been reported to have antiproliferative effects on trypanosoma cruzi however, the mechanism of protozoan action of egcg has not been studied. in the present study, we demonstrate the mechanism for the antileishmanial activity of egcg against leishmania amazonensis promastigotes. incubation with egcg significantly inhibited l. amazonensis promastigote proliferation in a time- and dose-dependent manner. the ic(50) for ... | 2012 | 22735546 |
| tomatidine promotes the inhibition of 24-alkylated sterol biosynthesis and mitochondrial dysfunction in leishmania amazonensis promastigotes. | leishmaniasis is a set of clinically distinct infectious diseases caused by leishmania, a genus of flagellated protozoan parasites, that affects ~12 million people worldwide, with ~2 million new infections annually. plants are known to produce substances to defend themselves against pathogens and predators. in the genus lycopersicon, which includes the tomato, l. esculentum, the main antimicrobial compound is the steroidal glycoalkaloid α-tomatine. the loss of the saccharide side-chain of tomati ... | 2012 | 22716777 |
| the abl and arg kinases mediate distinct modes of phagocytosis and are required for maximal leishmania infection. | leishmania, an obligate intracellular parasite, binds several receptors to trigger engulfment by phagocytes, leading to cutaneous or visceral disease. these receptors include complement receptor 3 (cr3), used by promastigotes, and the fc receptor (fcr), used by amastigotes. the mechanisms mediating uptake are not well understood. here we show that abl family kinases mediate both phagocytosis and the uptake of leishmania amazonensis by macrophages (ms). imatinib, an abl/arg kinase inhibitor, decr ... | 2012 | 22665498 |
| morita-baylis-hillman adducts: biological activities and potentialities to the discovery of new cheaper drugs. | this review aims to present by the first time the morita-baylis-hillman adducts (mbha) as a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs. now, most these compounds can be prepared fast and on a single synthetic step (one-pot reaction) in high yields and using ecofriendly synthetic protocols. we highlight here the aromatic mbha, which have shown diverse biological activities as anti-leishmania chagasi and leishmania amazonen ... | 2012 | 22632793 |
| in vitro and in vivo activity of a palladacycle complex on leishmania (leishmania) amazonensis. | antitumor cyclopalladated complexes with low toxicity to laboratory animals have shown leishmanicidal effect. these findings stimulated us to test the leishmanicidal property of one palladacycle compound called dppe 1.2 on leishmania (leishmania) amazonensis, an agent of simple and diffuse forms of cutaneous leishmaniasis in the amazon region, brazil. | 2012 | 22616018 |
| exposure of phosphatidylserine on leishmania amazonensis isolates is associated with diffuse cutaneous leishmaniasis and parasite infectivity. | diffuse cutaneous leishmaniasis (dcl) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. in brazil, leishmania (leishmania) amazonensis is the main species involved in dcl cases. in the experimental model, recognition of phosphatidylserine (ps) molecules exposed on the surface of amastigotes forms of l. amazonensis inhibits the inflammatory response of infected macrophages as a strategy to ev ... | 2012 | 22574191 |
| subversion and utilization of host innate defense by leishmania amazonensis. | infection with leishmania amazonensis and other members of the leishmania mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. diffuse cutaneous leishmaniasis (cl) is a rare but severe form, and its clinical hallmark is excessive parasitic growth in infected cells accompanied by profound impairments in host immune responses to the parasites. since these parasites also cause non-healing cl in most inbred ... | 2012 | 22566939 |
| activity of cuban plants extracts against leishmania amazonensis. | natural products have long been providing important drug leads for infectious diseases. leishmaniasis is a major health problem worldwide that affects millions of people especially in the developing nations. there is no immunoprophylaxis (vaccination) available for leishmania infections, and conventional treatments are unsatisfactory; therefore, antileishmanial drugs are urgently needed. in this work, 48 alcoholic extracts from 46 cuban plants were evaluated by an in vitro bioassay against leish ... | 2012 | 22530133 |
| subversion of immunity by leishmania amazonensis parasites: possible role of phosphatidylserine as a main regulator. | leishmania amazonensis parasites cause progressive disease in most inbred mouse strains and are associated with the development of diffuse cutaneous leishmaniasis in humans. the poor activation of an effective cellular response is correlated with the ability of these parasites to infect mononuclear phagocytic cells without triggering their activation or actively suppressing innate responses of these cells. here we discuss the possible role of phosphatidylserine exposure by these parasites as a m ... | 2012 | 22518276 |
| dihydrochalcones and benzoic acid derivatives from piper dennisii. | two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin c (3), 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), 4,2',6'-trihydroxy-4'-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2h-1-chromene-6-carboxylic acid (9), and 3-(3',7'-dimethyl-2',6'-octadienyl)-4-methoxybenzoic ... | 2012 | 22516933 |
| the stepwise selection for ketoconazole resistance induces upregulation of c14-demethylase (cyp51) in leishmania amazonensis. | ketoconazole is a clinically safe antifungal agent that also inhibits the growth of leishmania spp. a study was undertaken to determine whether leishmania parasites are prone to becoming resistant to ketoconazole by upregulating c14-demethylase after stepwise pharmacological pressure. leishmania amazonensis promastigotes [inhibitory concentration (ic)₅₀ = 2 µm] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, la8 (ic₅₀ = 8 µm) and la10 (ic₅₀ = 10 µm). ... | 2012 | 22510839 |
| leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity. | in leishmania, de novo polyamine synthesis is initiated by the cleavage of l-arginine to urea and l-ornithine by the action of arginase (arg, e.c. 3.5.3.1). previous studies in l. major and l. mexicana showed that arg is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. the arg protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. first, the l ... | 2012 | 22479507 |
| miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of c57bl/6 mice. | miltefosine is an anticancer drug currently used to treat visceral and cutaneous leishmaniasis, also presents a broad-spectrum of fungicidal and antiamoebae activities. it acts on the metabolism of phospholipids and glycoproteins of the membrane of parasites. our study aimed to evaluate the effects of miltefosine (0.4 to 50.0 μg/ml) on the phagocytosis and nitric oxide production by macrophages of c57bl/6 mice to clarify the immunomodulatory effects of the drug on macrophages of c57bl/6, strain ... | 2012 | 22465961 |
| leishmania amazonensis: inhibition of 3'-nucleotidase activity by cu2+ ions. | free cu(2+) is toxic due to the capacity of free copper ions to catalyze the production of reactive oxygen species (ros) that can modify the structure and/or function of biomolecules. in addition, non-specific binding to enzymes, which modifies their catalytic activities, can occur. in this work, the mechanisms underlying the ability of copper to inhibit 3'-nucleotidase from leishmania amazonensis (la3'-nucleotidase) were investigated. to that end, la3'-nucleotidase activity was assayed with cuc ... | 2012 | 22449511 |
| in vitro leishmanicidal activity of n-dodecyl-1,2-ethanediamine. | polyamine biosynthesis and inhibition in parasites have been an attractive chemotherapeutic approach in the design of novel antiparasitic drugs. we study in this work the effect of n-dodecyl-1,2-ethylenediamine (ndde) on the morphology and replication of leishmania using macrophages cultured from the peritoneal exudate of mice infected in vitro with three species of leishmania: leishmania (leishmania) amazonensis, leishmania (viannia) brasiliensis and leishmania (leishmania) chagasi. the results ... | 2012 | 22440898 |
| promotion of a functional b cell germinal center response after leishmania species co-infection is associated with lesion resolution. | co-infection of c3heb/fej (c3h) mice with both leishmania major and leishmania amazonensis leads to a healed footpad lesion, whereas co-infection of c57bl/6 (b6) mice leads to non-healing lesions. this inability to heal corresponds to a deficiency in b cell stimulation of the macrophage-mediated killing of l. amazonensis in vitro and a less robust antibody response. the mechanism that leads to healing of these lesions is not completely known, although our studies implicate the b cell response as ... | 2012 | 22429963 |
| antibacterial and antiparasitic effects of bothropoides lutzi venom. | the therapeutic potential of toxins has aroused great interest in the scientific community. microbial resistance is a serious current public health problem, in part because of the wide use of antimicrobial drugs. furthermore, there are several problems in the treatment of parasitic diseases such as leishmaniosis and chagas' disease, including the low efficacy in some clinical phases of the diseases and the loss of effectiveness of benzonidazole in the chronic phase of chagas' disease. in this co ... | 2012 | 22428250 |
| kinetoplastid membrane protein-11 exacerbates infection with leishmania amazonensis in murine macrophages. | in leishmania amazonensis, kinetoplastid membrane protein-11 (kmp-11) expression increases during meta-cyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. we show that the addition of kmp-11 exacerbates l. amazonensis infection in peritoneal macrophages from balb/c mice by increasing interleukin (il)-10 secretion and arginase activity while reducing nitric oxide (no) production. the doses of kmp-11, the il-10 ... | 2012 | 22415264 |