| direct evidence for role of anti-saliva antibodies against salivary gland homogenate of p. argentipes in modulation of protective th1-immune response against leishmania donovani. | currently the main concerns regarding control of visceral leishmaniasis (vl) caused by l. donovani are immunosuppression, relating toxicity of anti-leishmanial drug and little development in appropriate vaccine and vector (p. argentipes) control. reports available from ex-vivo studies reflect significance of vector salivary gland homogenate (sgh) in reverting immunosuppression of infected vl subjects and as such the immunogenic nature of sgh can be a strategy to modulate immune system and anti-l ... | 2016 | 27484246 |
| leishmania donovani-induced prostaglandin e2 generation is critically dependent on host toll-like receptor 2-cytosolic phospholipase a2 signaling. | visceral leishmaniasis (vl) is the second-largest parasitic killer disease after malaria. during vl, the protozoan leishmania donovani induces prostaglandin e2 (pge2) generation within host macrophages to aid parasite survival. pge2 significantly influences leishmanial pathogenesis, as l. donovani proliferation is known to be attenuated in pge2-inhibited macrophages. here, we report for the first time that signaling via macrophage toll-like receptor 2 (tlr2) plays an instrumental role in inducin ... | 2016 | 27481248 |
| arylthiosemicarbazones as antileishmanial agents. | based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. a series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of leishmania donovani. from these, 22 compounds showed ec50 values below 10 μm with the most active de ... | 2016 | 27475107 |
| optimizing immunization strategies for the induction of antigen-specific cd4 and cd8 t cell responses for protection against intracellular parasites. | immunization strategies that generate either cd4 or cd8 t cell responses are relatively well described, but less is known with regard to optimizing regimens to induce both cd4 and cd8 memory t cells. considering the importance of both cd4 and cd8 t cells in the control of intracellular pathogens such as leishmania donovani, we wanted to identify vaccines that could raise both cd4 and cd8 t cell responses and determine how to configure immunization strategies to generate the best combined protect ... | 2016 | 27466350 |
| microrna expression profiling of leishmania donovani-infected host cells uncovers the regulatory role of mir30a-3p in host autophagy. | leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (pv) of the monocyte/macrophage lineage. it reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. micrornas (mirnas), a class of small 22 to 24 nucleotide noncoding regulatory rnas alter the gene expression and consequently proteome output by targeting mrnas, may play a regulatory role in modulating host cell functions. in the pr ... | 2016 | 27459332 |
| volatile oil profile of some lamiaceous plants growing in saudi arabia and their biological activities. | a comparative investigation of hydro-distilled essential oils from aerial parts of mentha longifolia l. (ml), mentha microphylla k.koch (mm), mentha australis r.br. (ma), and teucrium polium l. (tp) growing in al madinah al munawwarah, saudi arabia, was carried out. the total numbers of identified constituents were 22, 23, 14, and 20 in ml, mm, ma, and tp oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. pulegone (40.7%) and cineole (33.4%) were the major ... | 2017 | 27458662 |
| loop-mediated isothermal amplification assay as a sensitive diagnostic tool for leishmania donovani infections in sri lanka. | cutaneous leishmaniasis (cl) in sri lanka is caused by leishmania donovani mon 37. confirmation of diagnosis is done through microscopy, either directly or after in vitro culture. molecular diagnostic methods are sensitive, but require well established laboratories. loop mediated isothermal amplification assay (lamp) is rapid, specific for parasite speciesspecific dna amplification, and requires only basic laboratory equipment. the aim of the study was to determine the potential utility of lamp ... | 2016 | 27423747 |
| ongoing outbreak of cutaneous leishmaniasis in northwestern yemen: clinicoepidemiologic, geographic, and taxonomic study. | cutaneous leishmaniasis (cl) is widespread in yemen but has not been fully documented. | 2016 | 27419356 |
| evaluation of s.c. route of immunization by homologous radio attenuated live vaccine in experimental murine model of visceral leishmaniasis. | our previous studies in balb/c mice showed substantial protection against the experimental murine visceral leishmaniasis (mvl) when the animals were immunized with γ-irradiated live leishmania donovani parasites through intra peritoneal (i.p.) and intra muscular (i.m.) routes respectively. the observations encouraged us to check the prophylactic efficacy of subcutaneous (s.c.) route as it is better alternative for human trial. the mice immunized with two subsequent doses of the radio attenuated ... | 2016 | 27413317 |
| molecular detection of infection homogeneity and impact of miltefosine treatment in a syrian golden hamster model of leishmania donovani and l. infantum visceral leishmaniasis. | control of visceral leishmaniasis caused by leishmania infantum and leishmania donovani primarily relies on chemotherapy using an increasingly compromised repertoire of antileishmanial compounds. for evaluation of novel drugs, the syrian golden hamster is considered as a clinically relevant laboratory model. in this study, two molecular parasite detection assays were developed targeting cathepsin-like cysteine protease b (cpb) dna and 18s rrna to achieve absolute amastigote quantification in the ... | 2016 | 27412759 |
| immunoprotective effect of lentinan in combination with miltefosine on leishmania-infected j-774a.1 macrophages. | rejuvenation of deteriorated host immune functions is imperative for successful annihilation of leishmania parasites. the use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. we herein investigated the immunostimulatory potency of a β-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on leishmania-infected j-774a.1 macrophages. our study shows ... | 2016 | 27387601 |
| molecular and serological evidence of leishmania infection in stray dogs from visceral leishmaniasis-endemic areas of bangladesh. | visceral leishmaniasis (vl), or kala-azar, is mainly caused by two closely related leishmania species, leishmania infantum and leishmania donovani leishmania infantum is responsible for zoonotic vl, with dogs as the main reservoir host in the mediterranean, the middle east, asia, and south america. in the indian subcontinent, vl is caused by l. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. the role of domestic and stray dogs in vl ... | 2016 | 27382083 |
| twin attributes of tyrosyl-trna synthetase of leishmania donovani: a housekeeping protein translation enzyme and a mimic of host chemokine. | aminoacyl-trna synthetases (aarss) are housekeeping enzymes essential for protein synthesis. apart from their parent aminoacylation activity, several aarss perform non-canonical functions in diverse biological processes. the present study explores the twin attributes of leishmania tyrosyl-trna synthetase (ldtyrrs) namely, aminoacylation, and as a mimic of host cxc chemokine. leishmania donovani is a protozoan parasite. its genome encodes a single copy of tyrosyl-trna synthetase. we first tested ... | 2016 | 27382051 |
| corrigendum: leishmanicidal activity of piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by th1 immunostimulatory potential in vivo. | [this corrects the article on p. 1368 in vol. 6, pmid: 26696979.]. | 2016 | 27379073 |
| 2.8-å cryo-em structure of the large ribosomal subunit from the eukaryotic parasite leishmania. | leishmania is a single-cell eukaryotic parasite of the trypanosomatidae family, whose members cause an array of tropical diseases. the often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs, and emerging resistant strains, underline the need to develop strategies to combat these pathogens. the trypanosomatid ribosome has recently been highlighted as a promising therapeutic target due to structural features that are distinct from other eukaryotes. he ... | 2016 | 27373148 |
| tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired ifn-γ production by spleen cells from human visceral leishmaniasis patients. | the pro-inflammatory cytokine tumor necrosis factor (tnf)-α has an important role in control of experimental leishmania donovani infection. less is known about the role of tnf-α in human visceral leishmaniasis (vl). evidence for a protective role is primarily based on case reports of vl development in individuals treated with tnf-α neutralizing antibody. in this study, we have evaluated how tnf-α neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (sa ... | 2016 | 27372917 |
| gmp reductase and genetic uncoupling of adenylate and guanylate metabolism in leishmania donovani parasites. | purine acquisition is an essential nutritional process for leishmania. although purine salvage into adenylate nucleotides has been investigated in detail, little attention has been focused on the guanylate branch of the purine pathway. to characterize guanylate nucleotide metabolism in leishmania and create a cell culture model in which the pathways for adenylate and guanylate nucleotide synthesis can be genetically uncoupled for functional studies in intact cells, we created and characterized n ... | 2016 | 27343371 |
| molecular detection, identification and phylogenetic inference of leishmania spp. in some desert lizards from northwest china by using internal transcribed spacer 1 (its1) sequences. | leishmaniasis caused by leishmania is still endemic in northwest china. it has been thought that reptiles could be a reservoir for mammalian leishmaniasis. however, data are still scarce on natural infection of lizards with leishmania spp. in china. the present study deals with detection, identification and phylogenetic inference of leishmania parasites at species and intraspecies levels isolated from six desert lizard species from 10 geographical locations in northwest china using amplification ... | 2016 | 27338182 |
| corrigendum: identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors. | | 2016 | 27323004 |
| plumbagin, a plant-derived naphthoquinone metabolite induces mitochondria mediated apoptosis-like cell death in leishmania donovani: an ultrastructural and physiological study. | naphthoquinones are known to exhibit a broad range of biological activities against microbes, cancer and parasitic diseases and have been widely used in indian traditional medicine. plumbagin is a plant-derived naphthoquinone metabolite (5-hydroxy-2-methyl-1,4-naphthoquinone) reported to inhibit trypanothione reductase, the principal enzyme and a validated drug target involved in detoxification of oxidative stress in leishmania. here, we report the mechanistic aspects of cell death induced by pl ... | 2016 | 27315817 |
| activity of a novel sulfonamide compound 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide against leishmania donovani. | new treatments for visceral leishmaniasis, caused by leishmania donovani, are needed to overcome sustained toxicity, cost, and drug resistance. the aim of this study was to evaluate the therapeutic effects of 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide (2nb) against promastigote and amastigote forms of l. donovani and examine its effect in combination with amphotericin b (amb) against amb-resistant clinical isolates. effects were assessed against extracellular promastigotes in vitro and int ... | 2016 | 27307706 |
| association of hla class i and ii genes with cutaneous leishmaniasis: a case control study from sri lanka and a systematic review. | the outcome of leishmaniasis is an interplay between leishamania and the host. identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. leishmaniasis is caused exclusively by l. donovani in sri lanka with localized cutaneous leishmaniasis (lcl) being the predominant form. we report here an association study of human leucocyte antigen (hla) class i and ii genes with lcl in sri lanka, the first on hla associations in cutaneous le ... | 2016 | 27301744 |
| pi inhibits intracellular accumulation of methylglyoxal in promastigote form of l. donovani. | similar to their mammalian counterpart, protozoan parasites including leishmania donovani detoxify methylglyoxal (mg),(1) a toxic ubiquitous product generated in glycolysis pathway. however, it differs in one or more way(s) from the humans. it is known that mg is eliminated either through glyoxalase (glo)(2) pathway and/or excreted across the cell membrane. this toxic metabolic by-product is known to be detoxified predominantly by the glo pathway and excretion across the cell membrane is never c ... | 2016 | 27297182 |
| optimization of loop-mediated isothermal amplification (lamp) assays for the detection of leishmania dna in human blood samples. | visceral leishmaniasis (vl), one of the most important neglected tropical diseases, is caused by leishmania donovani eukaryotic protozoan parasite of the genus leishmania, the disease is prevalent mainly in the indian sub-continent, east africa and brazil. vl can be diagnosed by pcr amplifying its1 and/or kdna genes. the current study involved the optimization of loop-mediated isothermal amplification (lamp) for the detection of leishmania dna in human blood or tissue samples. three lamp systems ... | 2016 | 27288706 |
| leishmania donovani aurora kinase: a promising therapeutic target against visceral leishmaniasis. | aurora kinases are key mitotic kinases executing multiple aspects of eukaryotic cell-division. the apicomplexan homologs being essential for survival, suggest that the leishmania homolog, annotated ldairk, may be equally important. | 2016 | 27288586 |
| integracides h-j: new tetracyclic triterpenoids from the endophytic fungus fusarium sp. | three new tetracyclic triterpenoids namely, integracides h (1), i (4), and j (5), along with integracides b (3) and f (2) have been isolated from the endophytic fungus fusarium sp. isolated from the roots of mentha longifolia l. (labiatae) growing in saudi arabia. the structure elucidation of the isolated compounds was achieved by spectroscopic analysis including uv, ir, 1d ((1)h and (13)c) and 2d ((1)h(1)h cosy, tocsy, hsqc, hmbc, and noesy) nmr as well as hresims and comparison with literature ... | 2016 | 27282207 |
| histone acetyltransferase hat4 modulates navigation across g2/m and re-entry into g1 in leishmania donovani. | histone acetyltransferases impact multiple processes. this study investigates the role of histone acetyltransferase hat4 in leishmania donovani. though hat4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with hat4-nulls experiencing an unusually long g2/m. survival of hat4-nulls in macrophages was also substantially compromised. dna microarray analysis revealed that hat4 modestly regulated the expression of only a select number of genes, thu ... | 2016 | 27272906 |
| innate immune b cell activation by leishmania donovani exacerbates disease and mediates hypergammaglobulinemia. | participation of b cells in the immune response by various antibody-independent mechanisms has recently been uncovered. b cells producing cytokines have been described for several infections and appear to regulate the adaptive immune response. b cell activation by leishmania donovani results in disease exacerbation. how leishmania activates b cells is still unknown. we show that l. donovani amastigotes activate b cells by triggering endosomal tlrs; this activation leads to the induction of vario ... | 2016 | 27264176 |
| a gcn2-like eif2α kinase (ldek1) of leishmania donovani and its possible role in stress response. | translation regulation in leishmania parasites assumes significance particularly because they encounter myriad of stresses during their life cycle. the eukaryotic initiation factor 2α (eif2α) kinases, the well-known regulators of translation initiation in higher eukaryotes have now been found to control various processes in these protozoan parasites as well. here, we report on cloning and characterization of a gcn2-like eif2α kinase from l. donovani and also on its modulation during nutrient sta ... | 2016 | 27248816 |
| identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors. | a library of arylidenefuropyridinediones was discovered as potent inhibitors of leishmania donovani topoisomerase 1 (ldtop1) where the active molecules displayed considerable inhibition with single digit micromolar ec50 values. this molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. the design was rationalized by molecular docking analysis of the compound prototype with human to ... | 2016 | 27221589 |
| the anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis. | there is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (vl). we report that delamanid (opc-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of leishmania donovani both in vitro and in vivo. twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of vl. treatment with lower doses revealed a u-shaped (hormetic) dose-response curve with greater parasite ... | 2016 | 27215734 |
| cholesterol corrects altered conformation of mhc-ii protein in leishmania donovani infected macrophages: implication in therapy. | previously we reported that kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. splenic macrophages (mφ) of leishmania donovani (ld) infected mice show decrease in membrane cholesterol, while ld infected macrophages (i-mφ) show defective t cell stimulating ability that could be corrected by liposomal delivery of cholesterol. t helper cells recognize peptide antigen in the context of class ii mhc molecule. it is known that the conformation o ... | 2016 | 27214205 |
| detection of leishmania donovani in peripheral blood of asymptomatic individuals in contact with patients with visceral leishmaniasis. | the majority of individuals infected with leishmania donovani complex remain asymptomatic. they may act as transmission reservoirs for visceral leishmaniasis (vl). we investigated sero-prevalence of l. donovani complex amongst those closely associated with patients with vl and whether these sero-reactive individuals had leishmania parasites in their peripheral blood. other risk factors were also investigated. | 2016 | 27198212 |
| chemical and antimicrobial profiling of propolis from different regions within libya. | extracts from twelve samples of propolis collected from different regions of libya were tested for their activity against trypanosoma brucei, leishmania donovani, plasmodium falciparum, crithidia fasciculata and mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. all the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of ec50 values between 1.65 and 53.6 μg/ml. the toxicity against mammalian cell ... | 2016 | 27195790 |
| purification and characterization of a novel intracellular sucrase enzyme of leishmania donovani promastigotes. | the promastigote stage of leishmania resides in the sand fly gut, enriched with sugar molecules. recently we reported that leishmania donovani possesses a sucrose uptake system and a stable pool of intracellular sucrose metabolizing enzyme. in the present study, we purified the intracellular sucrase nearly to its homogeneity and compared it with the purified extracellular sucrase. the estimated size of intracellular sucrase is ~112 kda by gel filtration chromatography, native page, and substrate ... | 2016 | 27190649 |
| elevated serum ada activity as a marker for diagnosis and prognosis of visceral leishmaniasis and post kala-azar dermal leishmaniasis in indian patients. | serum adenosine deaminase (ada) activity increases in diseases where cellular immunity is involved. since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ada activity in different pathological conditions. adenosine deaminase was determined in sera of active visceral leishmaniasis (vl) patients (n = 39), active postkala-azar dermal leishmaniasis (pkdl) cases (n = 3 ... | 2016 | 27186641 |
| supplementation of host response by targeting nitric oxide to the macrophage cytosol is efficacious in the hamster model of visceral leishmaniasis and adds to efficacy of amphotericin b. | we investigated efficacy of nitric oxide (no) against leishmania donovani. no is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. however, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. we incorporated diethylenetriamine no adduct (deta/no), a prodrug, into poly(lactide-co-glyc ... | 2016 | 27183429 |
| mobile suitcase laboratory for rapid detection of leishmania donovani using recombinase polymerase amplification assay. | leishmania donovani (ld) is a protozoan parasite transmitted to humans from sand flies, which causes visceral leishmaniasis (vl). currently, the diagnosis is based on presence of the anti-ld antibodies and clinical symptoms. molecular diagnosis would require real-time pcr, which is not easy to implement at field settings. in this study, we report on the development and testing of a recombinase polymerase amplification (rpa) assay for the detection of ld. | 2016 | 27177926 |
| structure- and ligand-based approaches to evaluate aporphynic alkaloids from annonaceae as multi-target agent against leishmania donovani. | leishmaniasis is a neglected disease that affects 15 million people around the world. many limitations are associated to the treatment as high cost and toxicity. several classes of natural substances with proven leishmanicidal activity were reported in the literature. phytochemsitry study of anaxagorea dolichocarpa (annonacea) reported the isolation of aporphine alkaloids. | 2016 | 27174814 |
| sla-pgn-primed dendritic cell-based vaccination induces th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of pkcβ. | emergence of drug resistance during visceral leishmaniasis (vl) is a major obstacle imposed during successful therapy. an effective vaccine strategy against this disease is therefore necessary. our present study exploited the sla (soluble leishmanial antigen) and pgn (peptidoglycan) stimulated bone marrow-derived dendritic cells (dcs) as a suitable vaccine candidate during experimental vl. sla-pgn-stimulated dcs showed a significant decrease in hepatic and splenic parasite burden, which were ass ... | 2016 | 27150838 |
| the contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis. | leishmania is a genus of protozoan parasites that give rise to a range of diseases called leishmaniasis that affects annually an estimated 1.3 million people from 88 countries. leishmania donovani and leishmania (l.) infantum chagasi are responsible to cause the visceral leishmaniasis. the parasite can use assorted strategies to interfere with the host homeostasis to establish persistent infections that without treatment can be lethal. in this review, we highlight the mechanisms involved in the ... | 2016 | 27148272 |
| structure-based virtual screening, molecular docking, admet and molecular simulations to develop benzoxaborole analogs as potential inhibitor against leishmania donovani trypanothione reductase. | visceral leishmaniasis (vl) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and pentamidine has been reported in the vl endemic region. amphotericin b has shown potential antileishmanial activity in different formulations but its cost of treatment and associated nephrotoxicity have limited its use by affected people living in the endemic zone. to control the vl infection ... | 2017 | 27147242 |
| application of rapid in vitro co-culture system of macrophages and t-cell subsets to assess the immunogenicity of dogs vaccinated with live attenuated leishmania donovani centrin deleted parasites (ldcen-/-). | live attenuated leishmania donovani parasites as ldcen(-/-) were shown to confer protective immunity against leishmania infection in mice, hamsters, and dogs. strong immunogenicity in dogs vaccinated with ldcen(-/-) has been previously reported, including increased antibody response favoring th1 response lymphoproliferative responses, cd4(+) and cd8(+) t-cells activation, increased levels of th1 and reduction of th2 cytokines, in addition to a significant reduction in parasite burden after 18 an ... | 2016 | 27136900 |
| quantitative proteome analysis of leishmania donovani under spermidine starvation. | we have earlier reported antileishmanial activity of hypericin by spermidine starvation. in the current report, we have used label free proteome quantitation approach to identify differentially modulated proteins after hypericin treatment. a total of 141 proteins were found to be differentially regulated with anova p value less than 0.05 in hypericin treated leishmania promastigotes. differentially modulated proteins have been broadly classified under nine major categories. increase in ribosomal ... | 2016 | 27123864 |
| differential role of leptin as an immunomodulator in controlling visceral leishmaniasis in normal and leptin-deficient mice. | visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani there are no vaccines and available drugs against leishmaniasis are toxic. immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. therefore, finding novel immunomodulators for vl therapy is a pressing need. this study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the imm ... | 2016 | 27114296 |
| genomic appraisal of the multifactorial basis for in vitro acquisition of miltefosine resistance in leishmania donovani. | protozoan parasites of the leishmania donovani complex are the causative agents of visceral leishmaniasis (vl), the most severe form of leishmaniasis, with high rates of mortality if left untreated. leishmania parasites are transmitted to humans through the bite of infected female sandflies (diptera: phlebotominae), and approximately 500,000 new cases of vl are reported each year. in the absence of a safe human vaccine, chemotherapy, along with vector control, is the sole tool with which to figh ... | 2016 | 27114280 |
| alkanediamide-linked bisbenzamidines are promising antiparasitic agents. | a series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two trypanosoma brucei (t.b.) subspecies: t.b. brucei and t.b. rhodesiense, trypanosoma cruzi, leishmania donovani and two plasmodium falciparum subspecies: a chloroquine-sensitive strain (nf54) and a chloroquine-resistant strain (k1). the in vitro cytotoxicity was determined against rat myoblast cells (l6). seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against bot ... | 2016 | 27104545 |
| mechanistic insight into the reactivation of bcaii enzyme from denatured and molten globule states by eukaryotic ribosomes and domain v rrnas. | in all life forms, decoding of messenger-rna into polypeptide chain is accomplished by the ribosome. several protein chaperones are known to bind at the exit of ribosomal tunnel to ensure proper folding of the nascent chain by inhibiting their premature folding in the densely crowded environment of the cell. however, accumulating evidence suggests that ribosome may play a chaperone role in protein folding events in vitro. ribosome-mediated folding of denatured proteins by prokaryotic ribosomes h ... | 2016 | 27099964 |
| antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds. | a small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. all tested compounds were active or moderately active against trypanosoma cruzi amastigotes in infected l6 cells and trypanosoma brucei brucei, four of eleven compounds were moderately active against leishmania donovani axenic parasites while none were deemed active against t. brucei rhodesiense. for the mo ... | 2016 | 27092415 |
| repeated training of accredited social health activists (ashas) for improved detection of visceral leishmaniasis cases in bihar, india. | accredited social health activists (ashas) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (vl). one of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and d ... | 2016 | 27077313 |
| correction: leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol. | | 2016 | 27073882 |
| a role for adenine nucleotides in the sensing mechanism to purine starvation in leishmania donovani. | purine salvage by leishmania is an obligatory nutritional process that impacts both cell viability and growth. previously, we have demonstrated that the removal of purines in culture provokes significant metabolic changes that enable leishmania to survive prolonged periods of purine starvation. in order to understand how leishmania sense and respond to changes in their purine environment, we have exploited several purine pathway mutants, some in which adenine and guanine nucleotide metabolism is ... | 2016 | 27062185 |
| apoptotic protein profile in leishmania donovani after treatment with hexaazatrinaphthylenes derivatives. | two hexaazatrinaphthylene derivatives, dgv-b and dgv-c previously known to induce an apoptotic-like process in leishmania donovani parasites were used in this study. for this purpose, two different human protein commercial arrays were used to determine the proteomic profile of the treated parasites compared to non-treated ones. one of the commercial arrays is able to detect the relative expression of 35 human apoptosis-related proteins and the other one is able to identify 9 different human kina ... | 2016 | 27060614 |
| comparative analysis of cellular immune responses in treated leishmania patients and hamsters against recombinant th1 stimulatory proteins of leishmania donovani. | our prior studies demonstrated that cellular response of t helper 1 (th1) type was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kda) of leishmania donovani promastigote, in treated leishmania patients as well as hamsters and showed significant prophylactic potential against experimental visceral leishmaniasis (vl). eighteen th1 stimulatory proteins were identified through proteomic analysis of this subfraction, out of which 15 were developed as recombinant proteins. in th ... | 2016 | 27047452 |
| febrifugine analogues as leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, admet and molecular dynamics simulation. | visceral leishmaniasis affects people from 70 countries worldwide, mostly from indian, african and south american continent. the increasing resistance to antimonial, miltefosine and frequent toxicity of amphotericin b drives an urgent need to develop an antileishmanial drug with excellent efficacy and safety profile. in this study we have docked series of febrifugine analogues (n = 8813) against trypanothione reductase in three sequential docking modes. extra precision docking resulted into 108 ... | 2017 | 27043972 |
| a replicative in vitro assay for drug discovery against leishmania donovani. | the protozoan parasite leishmania donovani is the causative agent of visceral leishmaniasis, a disease potentially fatal if not treated. current available treatments have major limitations, and new and safer drugs are urgently needed. in recent years, advances in high-throughput screening technologies have enabled the screening of millions of compounds to identify new antileishmanial agents. however, most of the compounds identified in vitro did not translate their activities when tested in in v ... | 2016 | 27021313 |
| structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents. | in an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. based on the reported x-ray structure of pteridine reductase 1 (ptr1) from leishmania major, we have designed a number of dihydropyrimidine-based derivatives to make specific interactions ... | 2016 | 27017551 |
| in vivo characterization of two additional leishmania donovani strains using the murine and hamster model. | leishmania donovani is a protozoan parasite causing the neglected tropical disease visceral leishmaniasis. one difficulty to study the immunopathology upon l. donovani infection is the limited adaptability of the strains to experimental mammalian hosts. our knowledge about l. donovani infections relies on a restricted number of east african strains (lv9, 1s). isolated from patients in the 1960s, these strains were described extensively in mice and syrian hamsters and have consequently become 're ... | 2016 | 27012562 |
| heat killed attenuated leishmania induces apoptosis of hepg2 cells through ros mediated p53 dependent mitochondrial pathway. | cytotoxic effect of attenuated leishmania on liver cancer cells by inducing ros generation. | 2016 | 27010918 |
| dna vaccine against visceral leishmaniasis: a promising approach for prevention and control. | the visceral leishmaniasis (vl) caused by leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. the arsenal of drugs available is limited, and resistance is common in clinical field isolates. therefore, vaccines could be an important alternative for prevention against vl. recently, some investigators advocated the protective efficacy of dna vaccines, which induces the t cell-based immunity against vl. the vaccine antigens are selected a ... | 2016 | 27009772 |
| laboratory diagnosis of human visceral leishmaniasis. | visceral leishmaniasis (vl), caused by the leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. vl patients may be asymptomatic or they may present symptoms and findings of a systemic infection. the positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic disease ... | 2016 | 27004573 |
| evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent. | leishmania donovani causes visceral leishmaniasis (vl), the second most deadly vector-borne parasitic disease. a recent epidemic in the indian subcontinent (isc) caused up to 80% of global vl and over 30,000 deaths per year. resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of l. donovani from the isc. we identify independent radiati ... | 2016 | 27003289 |
| one-pot synthesis and evaluation of antileishmanial activities of functionalized s-alkyl/aryl benzothiazole-2-carbothioate scaffold. | the synthesis of hitherto unreported s-alkyl/aryl benzothiazole-2-carbothioate is reported from thiols, oxalyl chloride, and 2-aminothiophenols using 10 mol % n-tetrabutylammonium iodide (tbai) as catalyst in acetonitrile through multicomponent reaction (mcr) strategy. the present protocol favored formation of benzothiazoles and thioesters via simultaneous formation of c-n and c-s bonds in good yields with a wide range of substrates. a few of the synthesized derivatives were evaluated for their ... | 2016 | 26999637 |
| an experimental challenge model of visceral leishmaniasis by leishmania donovani promastigotes in mice. | although visceral leishmaniasis is a fatal disease in humans and dogs, the use of mouse models is important for obtaining a better understanding of the pathogenesis, immunity, and host-parasite interactions of this disease. such models are also useful for the evaluation of vaccines and chemotherapies for treatment of visceral leishmaniasis. here, we present our method of experimental inoculation of mice with leishmania donovani promastigotes. nutrient-enriched undefined media may be beneficial f ... | 2016 | 26987675 |
| local production of a liquid direct agglutination test as a sustainable measure for control of visceral leishmaniasis in sudan. | a prerequisite for the control of visceral leishmaniasis (vl) is the accessibility to reference diagnostics. the high price of the freeze-dried direct agglutination test (fd-dat) and the short shelf-life time of the rk39 strip test (rk39) have limited the application of these tests in sudan. an original liquid dat (lq-dat) with high reproducibility compared with the fd-dat and rk39 has been routinely produced in our laboratory since 1999. in this study, a 3.4-year-old batch (of more than 90 test ... | 2016 | 26976890 |
| first molecular characterization of leishmania species causing visceral leishmaniasis among children in yemen. | visceral leishmaniasis (vl) is a debilitating, often fatal disease caused by leishmania donovani complex; however, it is a neglected tropical disease. l. donovani complex comprises two closely related species, l. donovani that is mostly anthroponotic and l. infantum that is zoonotic. differentiation between these two species is critical due to the differences in their epidemiology and pathology. however, they cannot be differentiated morphologically, and their speciation using isoenzyme-based me ... | 2016 | 26966902 |
| discovery of high affinity inhibitors of leishmania donovani n-myristoyltransferase. | n-myristoyltransferase (nmt) is a potential drug target in leishmania parasites. scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for leishmania donovani nmt; development led to high affinity inhibitors with excellent ligand efficiency. the binding mode was characterised by crystallography and provides a structural rationale for selectivity. | 2015 | 26962429 |
| mutational and structural analysis of conserved residues in ribose-5-phosphate isomerase b from leishmania donovani: role in substrate recognition and conformational stability. | ribose-5-phosphate isomerase b from leishmania donovani (ldrpib) is one of the potential drug targets against visceral leishmaniasis. in the present study, we have targeted several conserved amino acids for mutational analysis (i.e. cys69, his11, his102, his138, asp45, tyr46, pro47 and glu149) to gain crucial insights into their role in substrate binding, catalysis and conformational stability of the enzyme. all the eight ldrpib variants were cloned, sequenced, expressed and purified. c69s, h102 ... | 2016 | 26953696 |
| hemoglobin guided nanocarrier for specific delivery of amphotericin b to leishmania infected macrophage. | leishmania donovani being an intracellular parasite poses many challenges against the attempted chemotherapy. after the resistance towards the first line of antileishmanial drug, amphotericin b has been the treatment of choice against visceral leishmaniasis, a fatal tropical disease. however, unfavorable toxicity profile, severe side effects, prolonged parenteral administration procedure limits the use of amphotericin b. lack of available specific delivery system also makes this drug unsafe for ... | 2016 | 26945483 |
| hemophagocytosis in experimental visceral leishmaniasis by leishmania donovani. | hemophagocytosis is a phenomenon in which macrophages phagocytose blood cells. there are reports on up-regulated hemophagocytosis in patients with infectious diseases including typhoid fever, tuberculosis, influenza and visceral leishmaniasis (vl). however, mechanisms of infection-associated hemophagocytosis remained elusive due to a lack of appropriate animal models. here, we have established a mouse model of vl with hemophagocytosis. at 24 weeks after infection with 1 x 10(7) leishmania donova ... | 2016 | 26942577 |
| differential expression of mirna regulates t cell differentiation and plasticity during visceral leishmaniasis infection. | visceral leishmaniasis (vl) is a tropical neglected disease caused by leishmania donovani, results in significant mortality in the indian subcontinent. the plasticity of t cell proliferation and differentiation depends on microrna mediated gene regulation which leads th1/th2 or th17/treg type of immune response during human vl. this study depicts the identification of target immune signaling molecule and transcription factors, which play a role in t-cell proliferation and differentiation followe ... | 2016 | 26941729 |
| structure of leishmania donovani coronin coiled coil domain reveals an antiparallel 4 helix bundle with inherent asymmetry. | coiled coils are ubiquitous structural motifs that serve as a platform for protein-protein interactions and play a central role in myriad physiological processes. though the formation of a coiled coil requires only the presence of suitably spaced hydrophobic residues, sequence specificities have also been associated with specific oligomeric states. rhxxhe is one such sequence motif, associated with parallel trimers, found in coronins and other proteins. coronin, present in all eukaryotes, is an ... | 2016 | 26940672 |
| in vitro susceptibilities of wild and drug resistant leishmania donovani amastigotes to piperolactam a loaded hydroxypropyl-β-cyclodextrin nanoparticles. | leishmaniasis is an epidemic in various countries, and the parasite leishmania donovani is developing resistance against available drugs. in the present study the antileishmanial action of piperolactam a (pl), isolated after bioactivity guided fractionation from root extracts of piper betle was accentuated in detail. activity potentiation was achieved via cyclodextrin complexation. crude hydro-ethanolic extract (pb) and three fractions obtained from pb and fabricated pl-hydroxypropyl-β-cyclodext ... | 2016 | 26940000 |
| genetic manipulation of leishmania donovani to explore the involvement of argininosuccinate synthase in oxidative stress management. | reactive oxygen and nitrogen species (ros and rns) produced by the phagocytic cells are the most common arsenals used to kill the intracellular pathogens. however, leishmania, an intracellular pathogen, has evolved mechanisms to survive by counterbalancing the toxic oxygen metabolites produced during infection. polyamines, the major contributor in this anti-oxidant machinery, are largely dependent on the availability of l-arginine in the intracellular milieu. argininosuccinate synthase (ass) pla ... | 2016 | 26939071 |
| host resistance to visceral leishmaniasis: prevalence and prevention. | visceral leishmaniasis (vl) is a chronic parasitic disease caused by the vector-borne leishmania donovani and leishmania (l.) infantum chagasi parasites. the disease affects about 12 million humans in more than 90 countries worldwide. if not treated, the visceral form of leishmania infection is potentially fatal, yielding about 50000 deaths per year. in the vertebrate host, the leishmania species causing vl spread systematically to propagate in macrophage reservoirs distributed in the tissues of ... | 2016 | 26934623 |
| attenuated leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 mapk dependent phagosome maturation in leishmania donovani co-infected macrophages. | promastigote form of leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. but till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict leishmania growth. attenuated leishmania strain exposed raw 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. the augmentation of pro-inflammatory activity is mostly attributed to p38 mapk and p44/42 mapk. in our study, these ac ... | 2016 | 26928472 |
| understanding the importance of conservative hypothetical protein ldbpk_070020 in leishmania donovani and its role in subsistence of the parasite. | the genome of leishmania donovani, the causative agent of visceral leishmaniasis, codes for approximately 65% of both conserved and non-conserved hypothetical proteins. studies on 'conserved hypothetical' proteins are expected to reveal not only new and crucial aspects of leishmania biochemistry, but it could also lead to discovery of novel drug candidates. conserved hypothetical protein, ldbpk_070020, is a 31.14 kda protein, encoded by an 810 bp gene. blast analysis of ldbpk_070020, performed a ... | 2016 | 26926257 |
| antileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, taxodium distichum. | two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of taxodium distichum, collected in central ohio. the active subfraction from which all compounds isolated in this study were purified was tested in vivo using leishmania donovani-infected mice and was found to dose-dependently reduce the para ... | 2016 | 26905523 |
| repositioning antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for neglected tropical diseases: structure-activity studies on a preclinical candidate for visceral leishmaniasis. | 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (pa-824). phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of dndi-vl-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (vl). additional work was then conducted to delineate its essential structural features, aiming to improve solubility and ... | 2016 | 26901446 |
| visceral leishmaniasis: a forgotten epidemic. | visceral leishmaniasis (vl or kala-azar) is most endemic in asia and africa and commonly affects young children. it is usually caused by leishmania donovani or leishmania infantum that are transmitted by phlebotomine sand flies. transmission may be anthroponotic or zoonotic or both, depending on the endemic area. clinical features include fever, hepatosplenomegaly, weight loss and pancytopenia. younger age, malnutrition and immunosuppression (hiv infection, use of immunosuppressive drugs) are ri ... | 2016 | 26895806 |
| universal minicircle sequence binding protein of leishmania donovani regulates pathogenicity by controlling expression of cytochrome-b. | leishmania contains a concatenated mitochondrial dna, kdna. universal minicircle sequence binding protein (umsbp), a mitochondrial protein, initiates kdna replication by binding with a conserved universal minicircle sequence (ums) of kdna. here, we describe first time in l. donovani the regulation of dna binding activity of umsbp and the role of umsbp in virulence. | 2016 | 26889377 |
| successful therapy of murine visceral leishmaniasis with astrakurkurone, a triterpene isolated from the mushroom astraeus hygrometricus, involves the induction of protective cell-mediated immunity and tlr9. | in our previous report, we showed that astrakurkurone, a triterpene isolated from the indian mushroom astraeus hygrometricus (pers.) morgan, induced reactive oxygen species, leading to apoptosis in leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 μg/ml. the aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to ... | 2016 | 26883702 |
| combined immune therapy for the treatment of visceral leishmaniasis. | chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. immunoregulatory networks are established to prevent tissue damage caused by inflammation. although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. immune checkpoint blockade has recently been successfully employed to treat cancer. this strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tu ... | 2016 | 26872334 |
| characteristics of phlebotomine sandflies in selected areas of sri lanka. | cutaneous leishmaniasis (cl) is an endemic disease in sri lanka. studies on vector aspects, although important for better understanding of disease transmission dynamics, are still limited. the present study describes the species distribution and behavioral patterns of sandflies within selected disease-prevalent zones in the country. adult sandflies were collected from several field sites over a two-year duration in sri lanka using cattle-baited net traps, cdc light traps and manual methods. spec ... | 2015 | 26867357 |
| dynein clusters into lipid microdomains on phagosomes to drive rapid transport toward lysosomes. | diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule ... | 2016 | 26853472 |
| abietane-type diterpenoid amides with highly potent and selective activity against leishmania donovani and trypanosoma cruzi. | dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, leishmania donovani and trypanosoma cruzi, were assayed. the most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an ic50 value of 0.37 μm against l. donovani axenic amastigotes and an outstanding ... | 2016 | 26849852 |
| integrating ribosomal promoter vectors that offer a choice of constitutive expression profiles in leishmania donovani. | we have designed a novel series of integrating ribosomal rna promoter vectors with five incrementally different constitutive expression profiles, covering a 250-fold range. differential expression was achieved by placing different combinations of synthetic or leishmanial dna sequences upstream and downstream of the transgene coding sequence in order to modulate pre-mrna processing efficiency and mrna stability, respectively. all of the vectors have extensive multiple cloning sites, and versions ... | 2015 | 26844641 |
| accurate serodetection of asymptomatic leishmania donovani infection by use of defined antigens. | infection with leishmania donovaniis typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (vl), a deadly disease that threatens 200 million people in areas where it is endemic. while diagnosis of acute vl has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection, which can be 4 to 20 times more prevalent than active disease. a simple an ... | 2016 | 26842701 |
| identification of a diverse indole-2-carboxamides as a potent antileishmanial chemotypes. | a novel series of highly diverse indole-2-carboxamides was synthesized utilizing the isocyanide based multicomponent reaction (imcr)-post modification approach and were identified as potential antileishmanial chemotype. among the synthesized 18 analogues, 12 analogues exhibited better antileishmanial activity against intracellular amastigotes form of leishmania donovani (ic50 values of 0.6-7.5 μm) as compared to standard drugs miltefosine and sodium stibogluconate. the compounds were also non-to ... | 2016 | 26840364 |
| efficient one-pot synthesis, molecular docking and in silico adme prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents. | bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4-hydroxycoumarin and substituted aromatic aldehydes using succinimide-n-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of leishmania donovani. compounds 3a (ic50= 155 μg/ml), 3g (ic50= 157.5 μg/ml) and 3l (ic50= 150 μg/ml) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (ic50= 490 μg/ml). also, synthesized ... | 2015 | 26839526 |
| expression and purification of an engineered, yeast-expressed leishmania donovani nucleoside hydrolase with immunogenic properties. | leishmania donovani is the major cause of visceral leishmaniasis (kala-azar), now recognized as the parasitic disease with the highest level of mortality second only to malaria. no human vaccine is currently available. a 36 kda l. donovani nucleoside hydrolase (ldnh36) surface protein has been previously identified as a potential vaccine candidate antigen. here we present data on the expression of ldnh36 in pichia pastoris and its purification at the 20 l scale to establish suitability for futur ... | 2016 | 26839079 |
| 15d-prostaglandin j2 induced reactive oxygen species-mediated apoptosis during experimental visceral leishmaniasis. | 15-deoxy-delta (12,14)-prostaglandin j2 (15d-pgj2) is a potent bioactive lipid mediator, known to possess several roles in cell regulation and differentiation along with antimicrobial efficacy against different bacterial and viral infections. in the present study, we investigated the therapeutic efficacy and mechanism of action of 15d-pgj2 in vitro in leishmania donovani promastigotes and infected j774 macrophages, and in vivo in balb/c mice/golden hamster model of experimental visceral leishman ... | 2016 | 26830627 |
| induction of il-10 and tgfβ from cd4+cd25+foxp3+ t cells correlates with parasite load in indian kala-azar patients infected with leishmania donovani. | visceral leishmaniasis (vl) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. however, the direct association between different immunological correlates and parasite numbers remains largely unknown. | 2016 | 26829554 |
| deprivation of l-arginine induces oxidative stress mediated apoptosis in leishmania donovani promastigotes: contribution of the polyamine pathway. | the growth and survival of intracellular parasites depends on the availability of extracellular nutrients. deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. to further understand the relationship, the mechanistic role of l-arginine in regulation of redox mediated survival of leishmania donovani promastigotes was investigated. l-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferat ... | 2016 | 26808657 |
| leucine-684: a conserved residue of an amp-acetyl coa synthetase (acecs) from leishmania donovani is involved in substrate recognition, catalysis and acetylation. | amp-acetyl coa synthetase (amp-acecs) is a key enzyme which catalyzes the activation of acetate to acetyl coa, an important intermediate at the cross roads of various anabolic and catabolic pathways. multiple sequence alignment of leishmania donovani acecs with other organisms revealed the presence of a highly conserved leucine residue at 684 position which is known to be crucial for acetylation by protein acetyl transferases in other organisms. in an attempt to understand the role of leucine re ... | 2016 | 26794803 |
| design, synthesis and biological evaluation of 1,3,6-trisubstituted β-carboline derivatives for cytotoxic and anti-leishmanial potential. | in the present study, 23 derivatives of 1,3,6-trisubstituted β-carboline were synthesized and evaluated for cytotoxic potential against four human cancer cells, namely a-549, hela, hep g2 and mcf-7 as well as anti-leishmanial activity against leishmania donovani (mhom/80/in/dd8) promastigotes. among the studied compounds, compounds 13c and 13q showed potent cytotoxic activity better than the parent compound 10. for instance, compound 13c was found to be the most cytotoxic with ic50 of 4.72, 3.59 ... | 2016 | 26791014 |
| highly improved antiparasitic activity after introduction of an n-benzylimidazole moiety on protein farnesyltransferase inhibitors. | in our search for new protein farnesyltransferase inhibitors with improved antiparasitic activities, we modified our previously developed 3-arylthiophene series of inhibitors by replacing the thioisopropyl group by different substituted imidazolylmethanamino moieties. twenty four new derivatives were synthesized and evaluated against human and parasite farnesyltransferases, and their anti-parasitic activity was determined against plasmodium falciparum, trypanosoma brucei, trypanosoma cruzi, and ... | 2016 | 26774924 |
| detection of natural infection of leishmania donovani (kinetoplastida: trypanosomatidae) in phlebotomus argentipes (diptera: psychodidae) from a forest ecosystem in the western ghats, india, endemic for cutaneous leishmaniasis. | a new focus of transmission of leishmania donovani causing cutaneous manifestations (cl) was reported by us earlier, in the western ghats region of thiruvananthapuram district, kerala, india. 12,253 sand fly specimens, comprising of three species belonging to the genus phlebotomus (24.7%) and 16 species belonging to the genus sergentomyia (57.3%) were collected from the region during 2012-2014. among phlebotomus species, phlebotomus argentipes was found predominant (77.3%), followed by phlebotom ... | 2016 | 26774685 |
| suppression of host pten gene expression for leishmania donovani survival in indian visceral leishmaniasis. | lipid phosphatase, pten is amongst the host gene actively involved in determining disease susceptibility. expression of pten and other genes in vicinity egr1 &4e-bp1 were evaluated in splenic tissue before and after treatment in visceral leishmaniasis patients. lower expression of egr1 in correlation with pten suppressed 4e-bp1 gene in active cases. the higher levels of pten mrna expression post treatment confirmed its role in effective clearance of leishmania. therefore, it is hypothesized that ... | 2016 | 26774334 |
| leishmania infantum asparagine synthetase a is dispensable for parasites survival and infectivity. | a growing interest in asparagine (asn) metabolism has currently been observed in cancer and infection fields. asparagine synthetase (as) is responsible for the conversion of aspartate into asn in an atp-dependent manner, using ammonia or glutamine as a nitrogen source. there are two structurally distinct as: the strictly ammonia dependent, type a, and the type b, which preferably uses glutamine. absent in humans and present in trypanosomatids, as-a was worthy of exploring as a potential drug tar ... | 2016 | 26771178 |