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characterization of glycolytic enzymes--raldolase and renolase of leishmania donovani, identified as th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis.th1 immune responses play an important role in controlling visceral leishmaniasis (vl) hence, leishmania proteins stimulating t-cell responses in host, are thought to be good vaccine targets. search of such antigens eliciting cellular responses in peripheral blood mononuclear cells (pbmcs) from cured/exposed/leishmania patients and hamsters led to the identification of two enzymes of glycolytic pathway in the soluble lysate of a clinical isolate of leishmania donovani--enolase (ldeno) and aldola ...201424475071
biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs.visceral leishmaniasis (vl) is caused by the intracellular protozoan leishmania donovani complex. vl may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. the nutritional status of the patients with vl is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. changes in lipoproteins and plasma proteins may have major impacts in the host durin ...201424474015
disuccinyl betulin triggers metacaspase-dependent endonuclease g-mediated cell death in unicellular protozoan parasite leishmania donovani.the unicellular organism leishmania undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. here, we showed that 3-o,28-o-disuccinyl betulin (disb), a potent topoisomerase type ib inhibitor, induced parasitic cell death by generating oxidative stress. the characteristic feature of the death process resembled the programmed cell death (pcd) seen in higher eukaryotes. in the current study, the generation of reactive oxygen species (ros), followed b ...201424468787
alkyl galactofuranosides strongly interact with leishmania donovani membrane and provide antileishmanial activity.we investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e., octyl-β-d-galactofuranoside (compound 1), 6-amino-β-d-galactofuranoside (compound 2), 6-n-acetamido-β-d-galactofuranoside (compound 3), and 6-azido-β-d-galactofuranoside (compound 4), on leishmania donovani. their mechanism of action was explored using electron paramagnetic resonance spectroscopy (epr) and nuclear magnetic resonance (nmr), and ultrastructural alterations were analyzed by transmission electron ...201424468785
strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in india and nepal.asymptomatic persons infected with the parasites causing visceral leishmaniasis (vl) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. we assessed the risk of progression from infection to disease as a function of dat and rk39 serological titers.201424466361
deletion of vitamin c biosynthesis enzyme, arabino-1, 4-lactone oxidase in leishmania donovani results in increased pro-inflammatory responses from host immune cells.recently, we reported molecular characterization, localization and functional importance of arabino-1, 4-lactone oxidase (alo) enzyme from leishmania donovani that catalyses the last step in ascorbate biosynthesis pathway. vitamin c (l-ascorbic acid) is implicated in several crucial physiological processes. to elucidate the biological role of d-arabinono-γ-lactone oxidase in leishmania, we made l. donovani alo null mutant (δalo) by double targeted gene replacement. this mutant lacked alo activit ...201424456202
aptamer based, non-pcr, non-serological detection of chagas disease biomarkers in trypanosoma cruzi infected mice.chagas disease affects about 5 million people across the world. the etiological agent, the intracellular parasite trypanosoma cruzi (t. cruzi), can be diagnosed using microscopy, serology or pcr based assays. however, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. it is well documented that several parasite proteins called t. cruzi excreted secreted antigens (tesa) ...201424454974
molecular mechanisms of in vitro betulin-induced apoptosis of leishmania donovani.although leishmanial infections of humans occur globally, the major health impact lies in developing nations, thus, leishmaniases remain "neglected" diseases for new drugs development. multidrug resistance has been documented in most countries where leishmaniases is endemic. betulin is a widely available and affordable natural product exerting leishmanicidal activity at micromolar concentration. in this study, the molecular mechanisms of death that contribute to the anti-leishmanial activity of ...201424420777
leishmania donovani activates uncoupling protein 2 transcription to suppress mitochondrial oxidative burst through differential modulation of srebp2, sp1 and usf1 transcription factors.in order to reside and multiply successfully within the host macrophages, leishmania parasites impair the generation of cellular as well as mitochondrial reactive oxygen species (ros), which is a major host defense mechanism against any invading pathogen. mitochondrial uncoupling protein 2 (ucp2) is strongly induced in leishmania infection, both at mrna and protein levels, to suppress the mitochondrial ros generation. in the present study we have demonstrated that leishmania donovani infection i ...201424417972
new fluoranthene flun-550 as a fluorescent probe for selective staining and quantification of intracellular lipid droplets.a new class of live cell permeant, nontoxic fluoranthene-based fluorescent probe (flun-550) having a high stokes shift in aqueous medium has been discovered. it showed selective staining of lipid droplets (lds, dynamic cytoplasmic organelles) at a low concentration without background noise in in vitro live cell imaging of 3t3-l1 preadipocytes, j774 macrophages, mcf7 breast cancer cells, and single-celled, parasitic protozoa leishmania donovani promastigotes and in vivo nonparasitic soil nematode ...201424410145
in vitro screening test using leishmania promastigotes stably expressing mcherry protein.transgenic leishmania major and leishmania donovani axenic promastigotes constitutively expressing mcherry were used for in vitro antileishmanial drug screening. this method requires minimal sample manipulation and can be easily adapted to automatic drug tests, allowing primary high-throughput screenings without the need for expensive and sophisticated instruments.201424395225
post kala-azar dermal leishmaniasis following treatment with 20 mg/kg liposomal amphotericin b (ambisome) for primary visceral leishmaniasis in bihar, india.the skin disorder post kala-azar dermal leishmaniasis (pkdl) occurs in up to 10% of patients treated for visceral leishmaniasis (vl) in india. the pathogenesis of pkdl is not yet fully understood. cases have been reported in india following therapy with most available treatments, but rarely in those treated with liposomal amphotericin b (ambisome). between july 2007 and august 2012 with the support of the rajendra memorial research institute (rmri), médecins sans frontières (msf) supported a vl ...201424392171
five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin b (ambisome) for visceral leishmaniasis in bihar, india.visceral leishmaniasis (vl; also known as kala-azar) is an ultimately fatal disease endemic in bihar. a 2007 observational cohort study in bihar of 251 patients with vl treated with 20 mg/kg intravenous liposomal amphotericin b (ambisome) demonstrated a 98% cure rate at 6-months. between july 2007 and august 2012, médecins sans frontières (msf) and the rajendra memorial research institute (rmri) implemented a vl treatment project in bihar, india-an area highly endemic for leishmania donovani-usi ...201424392168
leishmania donovani targets tumor necrosis factor receptor-associated factor (traf) 3 for impairing tlr4-mediated host response.intramacrophage pathogen leishmania donovani escapes host immune response by subverting toll-like receptor (tlr) signaling, which is critically regulated by protein ubiquitination. in the present study, we identified tumor necrosis factor receptor-associated factor (traf) 3, degradative ubiquitination of which is essential for tlr4 activation, as a target for leishmania to deactivate lps-mediated tlr4 signaling. we used lps-treated raw 264.7 cells and compared the tlr4-mediated immune response i ...201424391131
serological survey and associated risk factors of visceral leish-maniasis in qom province, central iran.visceral leishmaniasis (vl) or kala-azar is considered as a parasitic disease caused by the species of leishmania donovani complex which is intracellular parasites. this systemic disease is endemic in some parts of provinc-es of iran. the aim of this study was to determine the seroprevalence of vl in qom province, central iran using di-rect agglutination test (dat).201426060679
efficacy of leishmania donovani trypanothione reductase, identified as a potent th1 stimulatory protein, for its immunogenicity and prophylactic potential against experimental visceral leishmaniasis.in visceral leishmaniasis (vl), th1-type of immune responses play an important role which correlates with recovery from and resistance to disease resulting in lifelong immunity. based on this rationale, the soluble leishmanial antigens that elicit cellular responses in peripheral blood mononuclear cells (pbmcs) from cured leishmania patients were characterized through immunoproteomic approach which led to the identification of trypanothione reductase (tpr) (a cytosolic enzyme explored as a drug ...201424370734
tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis.effect of pure herb, tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in leishmania donovani infected balb/c mice. administration of cisplatin (5mg/kg b.wt. daily for 5 days, i.p.) reduced the parasite load in l. donovani infected balb/c mice but produced damage in liver and kidney as manifested biochemically by an increase in serum glutamate oxaloacetate transaminase (sgot), serum glutamate pyruvate t ...201424370645
in vitro synergistic effect of amphotericin b and allicin on leishmania donovani and l. infantum.current monotherapy against visceral leishmaniasis has serious side effects, and resistant leishmania strains have been identified. amphotericin b (amb) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. results obtained showed, using a fixed-ratio analysis, that the combination of diallyl thiosulfinate (allicin) and amb ranged from moderately synergic to synergic at low concentrations (0.07 μm amb plus 35.45 μm all ...201424366748
the emergence of leishmania major and leishmania donovani in southern turkey.in southern turkey, leishmania tropica and l. infantum are both the causative agents of cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl), respectively. however, l. major and l. donovani were known to exist after the influx of syrian refugees.201424449479
comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant leishmania donovani.leishmania donovani is the causative agent of anthroponotic visceral leishmaniasis in the indian subcontinent. oral miltefosine therapy has recently replaced antimonials in endemic areas. however, the drug is at risk of emergence of resistance due to unrestricted use, and, already, there are indications towards decline in treatment efficacy. hence, understanding the mechanism of miltefosine resistance in the parasite is crucial. we employed genomic microarray analysis to compare the gene express ...201424449447
selective inhibition of leishmania donovani by active extracts of wild mushrooms used by the tribal population of india: an in vitro exploration for new leads against parasitic protozoans.the study was intended at evaluating the anti-proliferating effect of mushrooms used in traditional folklore of santal tribal population in india against leishmania donovani (mhom/in/83/ag83). a total of eighteen extracts, three estracts from each mushroom [(80% ethanol extracted; fa), (water-soluble polysaccharide fraction; fb), (polyphenolic fraction; fc)], from six wild mushrooms were obtained. these extracts were tested against the promastigotes and amastigotes for their antileishmanial capa ...201424440295
il-4 contributes to failure, and colludes with il-10 to exacerbate leishmania donovani infection following administration of a subcutaneous leishmanial antigen vaccine.visceral leishmaniasis caused by the protozoan parasite leishmania donovani complex is a potentially fatal disease if left untreated. few treatment options exist and are toxic, costly and ineffective against resistant strains. thus a safe and efficacious vaccine to combat this disease is needed. previously, we reported that intraperitoneal administration of leishmanial antigens (lag) entrapped in liposomes conferred protection to balb/c mice against l. donovani challenge infection. however, this ...201424428931
an actin-like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of leishmania donovani.actin-related proteins are ubiquitous actin-like proteins that show high similarity with actin in terms of their amino acid sequence and three-dimensional structure. however, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. here, we show that a novel actin-related protein (orf lmjf.13.0950) is localized mainly in the leishmania mitochondrion. we further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in t ...201424354789
comparison of pcr-based diagnoses for visceral leishmaniasis in bangladesh.the diagnosis of visceral leishmaniasis (vl) is performed using multiple methods encompassing parasitological, serological and nucleic acid-based diagnostic tools, each method with its own unique advantages and disadvantages. conventional parasitological methods are risky for the patient and require skilled personnel to collect specimens from spleen or bone marrow, and hence they are not generally available in impoverished areas. polymerase chain reaction (pcr) has been validated as an excellent ...201424333754
post-kala-azar dermal leishmaniasis mimicking leprosy relapse: a diagnostic dilemma.post-kala-azar dermal leishmaniasis (pkdl) is well recognized in the indian subcontinent and is not infrequently confused with leprosy. the present report describes findings in an unusual case of pkdl.201424321013
sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen porphyromonas gingivalis.a carbonic anhydrase (ca, ec 4.2.1.1) denominated pgica, belonging to the γ-class, from the oral pathogenic bacteria porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. dichlorophenamide, topiramate and many simple aromatic/heterocyclic sulfonamides were ineffective as pgica inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4 ...201424316122
triazino indole-quinoline hybrid: a novel approach to antileishmanial agents.a novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7-chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro activity against extracellular promastigote and intracellular amastigote form of leishmania donovani. among all tested compounds, compounds 7a and 7b were found to be the most active with ic50 values 1.11, 0.36μm and selectivity index (si) values 67, >1111, respectively, against amastigote form of l. donovani which is several folds more pote ...201424314395
leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (socs) proteins.one of the mechanisms for establishment of infection employed by intra-macrophage pathogen-like leishmania is inhibition of oxidative burst-mediated macrophage apoptosis to protect their niche for survival and replication. we tried to elucidate the underlying mechanism for this by using h2o2 for induction of apoptosis. leishmania donovani-infected macrophages were much more resistant to h2o2-mediated apoptosis compared with control. although infected cells were capable of comparable reactive oxy ...201424275663
stat4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis.we and others have previously shown that il-12 is indispensable for immunity and is required for the optimal antiparasitic activity of antimonials in experimental visceral leishmaniasis caused by leishmania donovani. here we investigated the role of stat4 in immunity against l. donovani using stat4 knockout mice and also determined the effect of stat4 deficiency in response to antimonial therapy. upon infection with l. donovani, stat4⁻/⁻ balb/c and c57bl/6 mice showed enhanced susceptibility to ...201424242758
exploring leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) as a potential drug target by biochemical, biophysical and inhibition studies.3-hydroxy-3-methylglutaryl-coa (hmg-coa) reductase (hmgr), an nadph dependant enzyme catalyzes the synthesis of mevalonic acid from hmg-coa required for isoprenoid biosynthesis. the hmgr gene from leishmania donovani was cloned and expressed. genome analysis of l. donovani revealed that hmgr gene having an open reading frame of 1305 bp encodes a putative protein of 434 amino acids. ldhmgr showed optimal activity at ph 7.2 and temperature 37 °c. kinetic analysis of this enzyme revealed km values ...201424239940
biomarkers for intracellular pathogens: establishing tools as vaccine and therapeutic endpoints for visceral leishmaniasis.visceral leishmaniasis in south asia is a serious disease affecting children and adults. acute visceral leishmaniasis develops in only a fraction of those infected individuals, the majority being asymptomatic with the potential to transmit infection and develop disease. we followed 56 individuals characterized as being asymptomatic by seropositivity with rk39 rapid diagnostic test in a hyperendemic district of bangladesh to define the utility of leishmania-specific antibodies and dna in identify ...201424237596
click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs.a series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(i)-catalyzed azide-alkyne cycloaddition (click chemistry). the newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the r isomer was determined by x-ray crystallography. ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against diff ...201424200958
asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo.current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. to overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. in this study we have evaluated a new therapeutic approach based on combination of asparagus race ...201424103199
to investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kda + mpl-a against leishmania donovani in balb/c mice.leishmaniasis has recently garnered attention as one of the diseases 'most neglected' by drug research and development, as the current therapeutic modalities available for the patients are ridden with unacceptable toxicity due to high dosage of the drug, prolonged treatment schedules, resistance and prohibitive costs. a successful chemotherapy requires a restoration of immune response; therefore, we combined leishmania-specific 78 kda antigen (with or without adjuvant mpl-a) along with a novel d ...201423964700
liposomal resiquimod for the treatment of leishmania donovani infection.the imidazoquinoline family of drugs are toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. we formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis.201423956375
antileishmanial activity evaluation of bis-lawsone analogs and dna topoisomerase-i inhibition studies.for the development of potent novel antileishmanial agents, 3,3'-(arylmethylene)bis(2-hydroxynaphthalene-1,4 dione) derivatives were synthesized from lawsone and evaluated for cytotoxicity on leishmania donovani promastigotes as well as on leishmanial dna topoisomerase-i. enzyme inhibition studies were conducted with simultaneous and preincubation conditions. total inhibition is compared to camptothecin (cpt), which was taken as positive control on both the systems of enzyme inhibition. the rang ...201423534930
nerve growth factor promotes killing of leishmania donovani by macrophages through the induction of hydrogen peroxide.visceral leishmaniasis is protozoonosis that occurs worldwide and still requires effective therapies with less toxicity. in this study, we examined the antileishmanial effect of nerve growth factor (ngf) using a murine infection model. ngf blocked the infection of macrophages by leishmania donovani, which was completely cancelled by a hydrogen peroxide inhibitor. in vivo, not only did ngf show antileishmanial effects, but combination therapy of ngf and sodium stibogluconate synergistically exhib ...201424937592
antigen-pulsed cpg-odn-activated dendritic cells induce host-protective immune response by regulating the t regulatory cell functioning in leishmania donovani-infected mice: critical role of cxcl10.visceral leishmaniasis (vl), caused by leishmania donovani, is a systemic infection of reticulo-endothelial system. there is currently no protective vaccine against vl and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphotericin b. in the present study, by using a murine model of leishmaniasis we evaluated the function played by soluble leishmanial antigen (sla)-pulsed cpg-odn-stimulated dendritic cells (sla-cpg-dcs) in re ...201424926293
atypical cutaneous leishmaniasis in the immunosuppressed.a 45-year-old woman, known case of seronegative arthritis and on immunosuppressive therapy, presented with a 2-week history of a macular lesion on the left calf that became papular and eventually ulcerated. the rest of the history was otherwise unremarkable and systemic examination did not reveal any abnormalities. the lesion was repeatedly biopsied but failed to reveal leishmania donovani bodies. concurrent leishmania igg was positive but igm was negative. leishmania igg confirmatory testing by ...201424916985
leishmania donovani eukaryotic initiation factor 5a: molecular characterization, localization and homology modelling studies.eukaryotic translation initiation factor 5a (eif5a) is a small acidic protein highly conserved from archaea to mammals. eif5a is the only protein which undergoes a unique lysine residue modification to hypusine. hypusinylation is important for the function of eif5a which is reported to be essential for cell viability. eif5a promotes formation of the first peptide bond at the onset of protein synthesis. however, its function in leishmania donovani is unclear. the present study focuses on the char ...201424909104
ubiquitination-mediated interaction among domains is responsible for inhibition of rna endonuclease activity of mrna cycling sequence binding protein from l. donovani (ldcsbp).in nearly complete absence of transcriptional regulation, messenger rna (mrna) turnover mediated through specific cis-elements plays a predominant role in the control of differential gene expression for the disease causing trypanosomatid parasites. in these organisms, the periodic accumulation of s-phase messages during cell cycle is determined by the presence of one or more copies of a conserved cauagaag octanucleotide motif in the untranslated regions of mrnas. in our previous studies, a multi ...201424908431
chemical- and thermal-induced unfolding of leishmania donovani ribose-5-phosphate isomerase b: a single-tryptophan protein.ribose-5-phosphate isomerase b (rpib), a crucial enzyme of pentose phosphate pathway, was proposed to be a potential drug target for visceral leishmaniasis. in this study, we have analyzed the biophysical properties of leishmania donovani rpib (ldrpib) enzyme to gain insight into its unfolding pathway under various chemical and thermal denaturation conditions by using fluorescence and cd spectroscopy. ldrpib inactivation precedes the structural transition at lower concentrations of both urea and ...201424907042
biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. a major shortcoming in the vaccine development against blood-borne parasitic agents such as leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extr ...201424904589
stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin b resistant leishmania donovani.kinetoplastids differ from other organisms in their ability to conjugate glutathione and spermidine to form trypanothione which is involved in maintaining redox homeostasis and removal of toxic metabolites. it is also involved in drug resistance, antioxidant mechanism, and defense against cellular oxidants. trypanothione synthetase (trys) of thiol metabolic pathway is the sole enzyme responsible for the biosynthesis of trypanothione in leishmania donovani. in this study, trys gene of l. donovani ...201424901644
hplc-based activity profiling for antiplasmodial compounds in the traditional indonesian medicinal plant carica papaya l.leaf decoctions of carica papaya have been traditionally used in some parts of indonesia to treat and prevent malaria. leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo.201424892830
studies on the antileishmanial mechanism of action of the arylimidamide db766: azole interactions and role of cyp5122a1.arylimidamides (aias) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. the aia db766 {2,5-bis[2-(2-i-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular leishmania parasites and is effective in murine and hamster models of visceral leishmaniasis when given orally, but its mechanism of action is unknown. in this study, through the use of continuous db766 pressure, we raised leishmania do ...201424890590
equilibrium unfolding of cyclophilin from leishmania donovani: characterization of intermediate states.cyclophilin from leishmania donovani (ldcyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase involved in a host of important cellular activities, such as signaling, heat shock response, chaperone activity, mitochondrial pore maintenance and regulation of hiv-1 infectivity. it also acts as the prime cellular target for the auto-immune drug cyclosporine a (csa). ldcyp is composed of a beta barrel encompassing the unique hydrophobic core of the molecule and is flanked by two helices (h1, h2) on ...201424887548
cytokine profiles amongst sudanese patients with visceral leishmaniasis and malaria co-infections.the immune system plays a critical role in the development of co-infections, promoting or preventing establishment of multiple infections and shaping the outcome of pathogen-host interactions. its ability to mediate the interplay between visceral leishmaniasis (vl) and malaria has been suggested, but poorly documented. the present study investigated whether concomitant infection with leishmania donovani complex and plasmodium falciparum in naturally co-infected patients altered the immunological ...201424886212
an inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial glycogen synthase kinase-3 over leishmanial cdc2-related protein kinase 3.in search of new antiparasitic agents for overcoming the limitations of current leishmaniasis chemotherapy, we have previously shown that 6-bromoindirubin-3'-oxime (6bio) and several other 6-substituted analogues of indirubin, a naturally occurring bis-indole present in mollusks and plants, displayed reverse selectivity from the respective mammalian kinases, targeting more potently the leishmanial cyclin-dependent kinase-1 (cdk1) homologue [cdc2-related protein kinase 3 (lcrk3)] over leishmanial ...201424886176
a dual luciferase system for analysis of post-transcriptional regulation of gene expression in leishmania.gene expression in kinetoplastid parasites is regulated via post-transcriptional mechanisms that modulate mrna turnover, translation rate, and/or post-translational protein stability. to facilitate the analysis of post-transcriptional regulation, a dual luciferase system was developed in which firefly and renilla luciferase reporters genetically fused to compatible drug resistance genes are integrated in place of one allele of the gene of interest and of an internal control gene, respectively, i ...201424878002
antileishmanial activity of a series of n²,n⁴-disubstituted quinazoline-2,4-diamines.a series of n(2),n(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against leishmania donovani and l. amazonensis intracellular amastigotes. a structure-activity and structure-property relationship study was conducted in part using the topliss operational scheme to identify new lead compounds. this study led to the identification of quinazolines with ec50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. q ...201424874647
synthesis and biological evaluation of chalcones as potential antileishmanial agents.antileishmanial activities of thirty-five synthetic chalcones have been examined. among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited potent in vitro activity (ic50 range from 1.70 to 8 μm) against extracellular promastigotes and intracellular amastigotes form of leishmania donovani. two promising compounds 22 and 37 were tested in vivo in l. donovani/hamster model. chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days whereas, 75.89% parasite ...201424858541
class ii mhc/peptide interaction in leishmania donovani infection: implications in vaccine design.we show that leishmania donovani-infected macrophages (mφs) are capable of stimulating mhc class ii (mhc-ii)-restricted t cells at 6 h of infection. at 48 h, infected mφs (i-mφs) failed to stimulate mhc-ii-restricted t cells but not mhc class i-restricted ones, in contrast to normal mφs. such i-mφs could stimulate t cells at a higher ag concentration, indicating that general ag processing and trafficking of peptide-mhc-ii complexes are not defective. analysis of the kinetic parameters, like "kon ...201424850723
coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against leishmania in hamsters by inducing th1-type immune responses.the aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(sa) coated nanocapsule (ncs) loaded with doxorubicin (sa-ncs-dox) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (ne-dox).201424837879
generation of growth arrested leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.visceral leishmaniasis (vl) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. vl is caused by the protozoan parasite leishmania donovani or leishmania infantum. although several second generation vaccines have been licensed to protect dogs against vl, there are no effective vaccines against human vl [1]. since people cured of leishmaniasis develop lifelong protection, development of live attenuated leishmania parasites as vaccines, which can have ...201424837513
efficacy of withania somnifera chemotypes nmitli - 101r, 118r and withaferin a against experimental visceral leishmaniasis.the immunoprophylactic and therapeutic potentials of root extracts of withania somnifera chemotypes (nmitli-118, nmitli-101) and pure withanolide-withaferin a was investigated against leishmania donovani infection in hamsters. the naive animals, fed orally with immunostimulatory doses of chemotypes 101r, 118r (10 and 3 mg/kg) and withaferin a (9 and 3 mg/kg) for five consecutive days and challenged with leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of p ...201424830833
deficiency of lymph node-resident dendritic cells (dcs) and dysregulation of dc chemoattractants in a malnourished mouse model of leishmania donovani infection.malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan leishmania donovani. we previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of l. donovani. in t ...201424818662
leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.leishmaniasis is a neglected tropical disease caused by leishmania species. it is a major health concern affecting 88 countries and threatening 350 million people globally. unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. the emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. the genome sequence of leishmania, provides access to novel genes that hold pot ...201424814525
the leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.during its life cycle, the protozoan pathogen leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. combining null mutant analysis with phosphorylation site-specific mutagenesis and functional complementation we genetically tested the requirement of the l. donovani chaperone cyclophilin 40 (ldcyp40) for infection. targeted replacement of ldcyp40 had no effect on parasite viabili ...201424811325
4-amino bis-pyridinium derivatives as novel antileishmanial agents.the antileishmanial activity of a series of bis-pyridinium derivatives that are analogues of pentamidine have been investigated, and all compounds assayed were found to display activity against promastigotes and intracellular amastigotes of leishmania donovani and leishmania major, with 50% effective concentrations (ec50s) lower than 1 μm in most cases. the majority of compounds showed similar behavior in both leishmania species, being slightly more active against l. major amastigotes. however, ...201424798287
trend analysis of visceral leishmaniasis at addis zemen health center, northwest ethiopia.visceral leishmaniasis (vl) is a systemic disease caused by the leishmania donovani complex. it is one of the fatal diseases if left untreated. in ethiopia, there are many vl endemic foci. the aim of this study was to determine the trends of vl in the study area.201424783211
shagenes a and b, new tricyclic sesquiterpenes produced by an undescribed antarctic octocoral.the isolation and characterization of two new tricyclic sesquiterpenoids, shagenes a (1) and b (2) are presented. these compounds were isolated from an undescribed soft coral collected from the scotia arc in the southern ocean. one- and two-dimensional nmr spectroscopy and mass spectrometry provided the data necessary to characterize the compounds and their relative stereochemical configurations. exploration of the bioactivity of shagenes a and b found 1 active against the visceral leishmaniasis ...201424779517
a comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.visceral leishmaniasis (vl) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. ninety per cent of vl cases occur in five countries namely bangladesh, india, nepal, sudan and brazil. no licensed vaccine is available till date against any form of leishmaniasis. high toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in vl endemic regions of the world. to ...201424747611
regulation dynamics of leishmania differentiation: deconvoluting signals and identifying phosphorylation trends.leishmania are obligatory intracellular parasitic protozoa that cause a wide range of diseases in humans, cycling between extracellular promastigotes in the mid-gut of sand flies and intracellular amastigotes in the phagolysosomes of mammalian macrophages. although many of the molecular mechanisms of development inside macrophages remain a mystery, the development of a host-free system that simulates phagolysosome conditions (37 °c and ph 5.5) has provided new insights into these processes. the ...201424741111
evaluation of leishmania donovani disulfide isomerase as a potential target of cellular immunity against visceral leishmaniasis.in leishmania species, protein disulfide isomerase (pdi) - a redox chaperone is primarily associated with virulence and survival. the precise mechanism, especially in relation to redox changes and its effects on immunological responses in visceral leishmaniasis (vl) is not completely understood as yet. therefore, we purified a recombinant pdi from leishmania donovani (r-ldpdi) which was of ∼15 kda molecular size and examined its effects on immunological responses in peripheral blood (pbmc) of hu ...201424732062
combination of liposomal cpg oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis.immuno-modulators in combination with antileishmanial drug miltefosine is a better therapeutic approach for treatment of visceral leishmaniasis (vl) as it not only reduces the dose of miltefosine but also shortens the treatment regimen. however, immunological mechanisms behind the perceived benefits of this combination therapy have not been investigated in detail. in the present study, we hypothesized that potential use of drugs that target the host in addition to the parasite might represent an ...201424732039
ketanserin, an antidepressant, exerts its antileishmanial action via inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) enzyme of leishmania donovani.leishmaniasis is one of the major health problems existing globally. the current chemotherapy for leishmaniasis presents several drawbacks like toxicity and increased resistance to existing drugs, and hence, there is a necessity to look out for the novel drug targets and new chemical entities. current trend in drug discovery arena is the "repurposing" of old drugs for the treatment of diseases. in the present study, an antidepressant, ketanserin, was found lethal to both leishmania donovani prom ...201424728519
design, synthesis, adme characterization and antileishmanial evaluation of novel substituted quinoline analogs.in vitro adme characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. compound 1 was highly permeable in intestinal pampa model (31 × 10(-6)cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. compound 1 was found to have no cyp450 liability with cyp2c9, 2 ...201424726804
[from unexplained fever to visceral leishmaniasis--a case report].visceral leishmaniasis or kala-azar is a systemic infectious vector-borne disease caused by protozoa leishmania donovani and leishmania infantum that are transmitted to mammalian hosts by sand flies. it occurrs sporadically in endemic areas, including mediterranean basin. southern coastal territories of croatia have been recognized as the foci of the disease. dogs are the main reservoir of human infection. clinical features include prolonged fever, malaise, hepatosplenomegaly, pancytopenia and i ...201424720151
flavone-resistant leishmania donovani overexpresses ldmrp2 transporter in the parasite and activates host mrp2 on macrophages to circumvent the flavone-mediated cell death.in parasites, atp-binding cassette (abc) transporters represent an important family of proteins related to drug resistance and other biological activities. resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed abc efflux pumps. progressively adapted baicalein (bln)-resistant parasites (pb(25)r) show overexpression of a novel abc transporter, which was classified as abcc2 or leishmania donovani mul ...201424706751
antiprotozoal activities of millettia richardiana (fabaceae) from madagascar.with at least 60% of the millettia species (fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of millettia richardiana. water and methanol crude extracts of the stem barks from m. richardiana and the six fractions resulting from the fractionation of the methanol extract were tested. the dichloromethane extracted fraction showed the best in vitro antiprotozoal activities (ic50=5.8 μg/ml against plasmodium falciparum, 11.8 μg/ml ...201424705564
no stress--hsp90 and signal transduction in leishmania.summary hsp90 (a.k.a. hsp83) plays a significant role in the life cycle control of the protozoan parasite leishmania donovani. rather than protecting leishmania spp. against adverse and stressful environs, hsp90 is required for the maintenance of the motile, highly proliferative insect stage, the promastigote. however, hsp90 is also essential for survival and proliferation of the intracellular mammalian stage, the amastigote. moreover, recent evidence shows hsp90 and other components of large mu ...201424703183
leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis.the use of live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver biologically active entities. thus, advancing our knowledge of such microbe-mediated therapy may suggest new avenues for therapeutic intervention in many diseases. we had earlier reported that the total lipid of attenuated leishmania donovani suppressed the inflammatory responses in rheumatoid arthritis patien ...201424696356
activity of olive leaf extracts against the promastigote stage of leishmania species and their correlation with the antioxidant activity.leishmaniasis is one of the neglected tropical diseases in terms of drug discovery and development. furthermore, the chemotherapy used to treat this disease has been proved to be highly toxic and to present resistance issues. as consequent, the need for novel leishmanicidal molecules has notably increased in the recent years. in the present work an attempt was made to evaluate the antioxidant and leishmanicidal activities besides presence of compounds in leaf extracts of 5 different tunisian oli ...201424662269
anti-l. donovani activity in macrophage/amastigote model of palmarumycin cp18 and its large scale production.palmarumycin cp18, isolated from an extract of the fermentation broth and mycelium of the panamanian endophytic fungus edenia sp., was previously reported with strong and specific activity against leishmania donovani. here we report that when the same strain was cultured on different solid media--harrold agar, leonian agar, potato dextrose agar (pda), corn meal agar, honey peptone agar, and eight vegetables (v8) agar--in order to determine the optimal conditions for isolation of palmarumycin cp1 ...201424660473
synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.antileishmanial activities of a library of synthetic chalcone analogues have been examined. among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of leishmania donovani. three promising compounds, 16, 17, and 22, were tested in a l. donovani/hamster model. oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, re ...201424635539
tissue requirements for establishing long-term cd4+ t cell-mediated immunity following leishmania donovani infection.organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by leishmania donovani. experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. cd4+ t cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. in this study, we show ...201424634490
a quantitative proteomic screen to identify potential drug resistance mechanism in α-difluoromethylornithine (dfmo) resistant leishmania donovani.visceral leishmaniasis (vl) caused by leishmania donovani is a systemic protozoan disease that is fatal if left untreated. the promastigote form of l. donovani is sensitive to growth inhibition by dl-α-difluoromethylornithine (dfmo), an inhibitor of ornithine decarboxylase (odc), the first enzyme of the polyamine biosynthetic pathway. exposure of a wild type (di700) cell population to gradually increasing concentrations of dfmo resulted in the selection of a strain of leishmania (dfmo-16), which ...201424631822
absence of leishmania infantum in cave bats in an endemic area in spain.though dogs have been historically considered the main reservoir of leishmania infantum, the role of wildlife in its epidemiology is attracting increasing attention. rodents, wild carnivores and, recently, hares (lepus spp.) have been proposed as sylvatic reservoirs for this parasite. bats have never been tested for l. infantum infection in europe. nevertheless, bats have a widespread distribution, they live in abundant colonies, and some species inhabit caves, where constant temperatures and hu ...201424623348
studies on the protective efficacy of second-generation vaccine along with standard antileishmanial drug in leishmania donovani infected balb/c mice.it is well established that visceral leishmaniasis (vl; also known as kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kda antigen with or without monophosphoryl lipid a (mpl-a) along wit ...201424618257
toll like receptor 2 and cc chemokine receptor 5 cluster in the lipid raft enhances the susceptibility of leishmania donovani infection in macrophages.in experimental visceral leishmaniasis the causative obligate protozoan parasite, l. donovani invades and multiplies inside of macrophages, one of the sentries of the mammalian immune system. the initial host-parasite interaction between the leishmania promastigote and the macrophage takes place at the plasma membrane interface. to trace any possible interaction between toll-like receptor 2 (tlr2) and cc chemokine receptor 5 (ccr5) during early leishmania-macrophage interactions, it was observed ...201424617012
experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of leishmania donovani and l. infantum.although widespread resistance of leishmania donovani and l. infantum against miltefosine (mil) and paromomycin (pmm) has not yet been demonstrated, both run the risk of resistance selection. unraveling the dynamics and mechanisms of resistance development is key to preserve drug efficacy in the field. in this study, resistance against pmm and mil was experimentally selected in vitro in intracellular amastigotes of several strains of both species with different antimony susceptibility background ...201424615359
bone marrow parasite burden among patients with new world kala-azar is associated with disease severity.kala-azar or visceral leishmaniasis, found mostly throughout the indian subcontinent, east africa, and brazil, kills 20,000-40,000 persons annually. the agents, leishmania donovani and leishmania infantum, are obligatory intracellular protozoa of mononuclear phagocytes found principally in the spleen and bone marrow. protracted fever, anemia, wasting, hepatosplenomegaly, hemorrhages, and bacterial co-infections are typical features. one hundred and twenty-two (122) in-hospital patients were stud ...201424615127
characterization of the proliferating cell nuclear antigen of leishmania donovani clinical isolates and its association with antimony resistance.previously, through a proteomic analysis, proliferating cell nuclear antigen (pcna) was found to be overexpressed in the sodium antimony gluconate (sag)-resistant clinical isolate compared to that in the sag-sensitive clinical isolate of leishmania donovani. the present study was designed to explore the potential role of the pcna protein in sag resistance in l. donovani. for this purpose, the protein was cloned, overexpressed, purified, and modeled. western blot (wb) and real-time pcr (rt-pcr) a ...201424614385
leishmania donovani: dynamics of l. donovani evasion of innate immune cell attack due to malnutrition in visceral leishmaniasis.malnutrition may be significant in the modulation of immune responses in visceral leishmaniasis (vl). data on the relationship between malnutrition and innate immune response in vl are limited. the aim of this study was to examine the effect of malnutrition on the profile of innate immune functions of polymorphonuclear neutrophil granulocytes (pmns) and monocytes through comparison of well-nourished and malnourished indian patients with vl.201424607302
development of targeted 1,2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin b for improved in vitro and in vivo effect in leishmaniasis.the principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (ps)-coated gelatin nanoparticles (gnps) bearing amphotericin b (amb) for specific targeting to the macrophages involved in visceral leishmaniasis (vl).201424606222
leishmania donovani infection causes distinct epigenetic dna methylation changes in host macrophages.infection of macrophages by the intracellular protozoan leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. the underlying molecular mechanisms involved remain largely unknown. in this study, we assessed epigenetic changes in macrophage dna methylation in response to infection with l. donovani as a possible mechanism for leishmania driven deactivation of host defense. we quantified and detected genome-w ...201425299267
new series of monoamidoxime derivatives displaying versatile antiparasitic activity.following the promising antileishmanial results previously obtained in monoamidoxime series, a new series of derivatives was synthesized using manganese(iii) acetate, wittig reactions and suzuki-miyaura cross coupling reactions. pharmacomodulation in r(1), r(2) or r(3) substituents on the amidoxime structure is shown to influence antiprotozoan activity in vitro: a monosubstituted phenyl group in r1 (32-35) led to an activity against leishmania donovani promastigotes (32, ic50 = 9.16 μm), whereas ...201425282267
comparative proteomics and glycoproteomics of plasma proteins in indian visceral leishmaniasis.visceral leishmaniasis (vl) is a deadly parasitic diseases caused by leishmania donovani; it is a major health problem in many countries. a lack of proper understanding of the disease biology, poor diagnostic methods and increasing drug resistance are the main reasons for the growing burden of vl infection. comparative plasma proteomics are a relatively useful technique that can be used to investigate disease-associated alterations that can help in understanding host responses against pathogens, ...201425276097
th1 stimulatory proteins of leishmania donovani: comparative cellular and protective responses of rtriose phosphate isomerase, rprotein disulfide isomerase and relongation factor-2 in combination with rhsp70 against visceral leishmaniasis.in visceral leishmaniasis, the recovery from the disease is always associated with the generation of th1-type of cellular responses. based on this, we have previously identified several th1-stimulatory proteins of leishmania donovani -triose phosphate isomerase (tpi), protein disulfide isomerase (pdi) and elongation factor-2 (el-2) etc. including heat shock protein 70 (hsp70) which induced th1-type of cellular responses in both cured leishmania patients/hamsters. since, hsps, being the logical t ...201425268700
a bioinformatics approach to reanalyze the genome annotation of kinetoplastid protozoan parasite leishmania donovani.leishmania donovani is a kinetoplastid protozoan parasite which causes the fatal disease visceral leishmaniasis in humans. genome sequencing of l. donovani revealed information about the arrangement of genes and genome architecture. after curation of the genome sequence, many genes in l. donovani were assigned as truncated or "partial" genes by the genome sequencing group. in the present study, we have carried out an extensive analysis and attempted to improve the gene models of these partial ge ...201425265881
new flavonol methyl ether from the leaves of vitex peduncularis exhibits potential inhibitory activity against leishmania donovani through activation of inos expression.one new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of vitex peduncularis wall and three known compounds from the leaves of methanol extract of vitex pinnata linn (verbenaceae) were isolated. the chemical structure of the new compound was established by detailed spectroscopic studies. the in vitro antileishmanial activities of 1 against both leishmania donovani promastigote and amastigote forms were evaluated. to characterize the effector mechan ...201425264585
quinone-amino acid conjugates targeting leishmania amino acid transporters.the aim of the present study was to investigate the feasibility of targeting leishmania transporters via appropriately designed chemical probes. leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (ldaap3 and ldaap7) to import these nutrients. probes 1-15 were originated by conjugating cytotoxic quinone fragments (ii and iii) with amino acids (i.e. arginine and lysine) by means of an amide linkage. the toxicit ...201425254495
the antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors.histone deacetylase inhibitors (hdaci) pleiotropy is largely due to their nonselective inhibition of various cellular hdac isoforms. connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting hdaci pleiotropy. the contribution of classes i and ii hdacs to the antileishmanial activity of hdaci was investigated using the amastigote and promastigote forms of leishmania donovani. we observed that the antileishmanial activities of hdaci are ...201425240614
novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against trypanosoma cruzi, the causative parasite of chagas disease. more importantly, several such analogs displayed significant antichagasic activity in vivo, superior to that of benznidazole, the current clinical standard. we now report the synthesis and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamid ...201425240098
structure-based design of potent and selective leishmania n-myristoyltransferase inhibitors.inhibitors of leishmania n-myristoyltransferase (nmt), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. crystal structures bound to leishmania major nmt were obtained, and the active diastereoisomer of one of the inhibitors was identified. on the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent leishmani ...201425238611
an imported case of cutaneous leishmaniasis caused by leishmania (leishmania) donovani in japan.leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. there have been few reports of leishmaniasis in japan and all were of foreign origin; therefore diagnosis is difficult for japanese physicians. there are 21 different pathogenic leishmania species, and identification is obtained by polymerase chain reaction (pcr). here we report an imported case of leishmaniasis by leishmania (leishmania) donovani infection from sri lanka. l. (l.) d ...201425228325
a soluble phosphodiesterase in leishmania donovani negatively regulates camp signaling by inhibiting protein kinase a through a two way process involving catalytic as well as non-catalytic sites.intracellular camp level and camp mediated responses are elevated when leishmania are exposed to macrophage phagolysosome conditions (37 °c and ph 5.5). phosphodiesterases play major role in camp regulation and in the present study we have cloned and characterized a 2.1 kb cytosolic isoform of phosphodiesterase from leishmania donovani (ldpded) which plays important role in camp homeostasis when the promastigotes are exposed to macrophage phagolysome conditions for converting to axenic amastigot ...201425310904
comparative lc-ms-based metabolite profiling of the ancient tropical rainforest tree symphonia globulifera.in the last few years, several phytochemical studies have been undertaken on the tropical tree symphonia globulifera leading to the isolation and characterisation of several compounds exhibiting antiparasitic activities against plasmodium falciparum, trypanosoma brucei and leishmania donovani. the comparative lc-ms based metabolite profiling study conducted on the tree led to the identification of compounds originating from specific tissues. the results showed that renewable organs/tissues can b ...201425301665
screening and characterization of rapd markers in viscerotropic leishmania parasites.visceral leishmaniasis (vl) is mainly due to the leishmania donovani complex. vl is endemic in many countries worldwide including east africa and the mediterranean region where the epidemiology is complex. taxonomy of these pathogens is under controversy but there is a correlation between their genetic diversity and geographical origin. with steady increase in genome knowledge, rapd is still a useful approach to identify and characterize novel dna markers. our aim was to identify and characteriz ...201425313833
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