| retraction: human recombinant migration inhibitory factor activates human macrophages to kill leishmania donovani. | | 2012 | 22956762 |
| extracts of artemisia annua leaves and seeds mediate programmed cell death in leishmania donovani. | leishmaniasis is one of the major tropical parasitic diseases, and the condition ranges in severity from self-healing cutaneous lesions to fatal visceral manifestations. there is no vaccine available against visceral leishmaniasis (vl) (also known as kala-azar in india), and current antileishmanial drugs face major drawbacks, including drug resistance, variable efficacy, toxicity and parenteral administration. we report here that n-hexane fractions of artemisia annua leaves (aal) and seeds (aas) ... | 2012 | 22956747 |
| identification of th1-responsive leishmanial excretory-secretory antigens (lesas). | the objective of this study was to evaluate the immunomodulatory role of leishmanial excretory-secretory antigens (lesas) released by in vitro cultured protozoan parasite leishmania donovani promastigotes. a total of seventeen excretory-secretory proteins of relative molecular weights 11, 13, 16, 18, 21, 23, 26, 29, 33, 35, 42, 51, 54, 58, 64, 70 and 80 kda were identified. the proteins were divided into five fractions (f1-f5) along with the whole lesas, these fractions were evaluated for their ... | 2012 | 22955114 |
| marchantin a, a macrocyclic bisbibenzyl ether, isolated from the liverwort marchantia polymorpha, inhibits protozoal growth in vitro. | in vitro anti-plasmodial activity-guided fractionation of a diethyl ether extract of the liverwort species marchantia polymorpha, collected in iceland, led to isolation of the bisbibenzyl ether, marchantin a. the structure of marchantin a (1) was confirmed by nmr and hreims. marchantin a inhibited proliferation of the plasmodium falciparum strains, nf54 (ic(50)=3.41μm) and k1 (ic(50)=2.02μm) and showed activity against other protozoan species trypanosoma brucei rhodesiense, t. cruzi and leishman ... | 2012 | 22951393 |
| drug-resistant microorganisms with a higher fitness--can medicines boost pathogens? | drug-resistant microorganisms (drms) are generally thought to suffer from a fitness cost associated with their drug-resistant trait, inflicting them a disadvantage when the drug pressure reduces. however, leishmania resistant to pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. this is likely due the combination of an intracellular pathogen and a drug that targets the parasite's general defense mechanisms while at the same time stimulating the host's ... | 2013 | 22950457 |
| development of luciferase expressing leishmania donovani axenic amastigotes as primary model for in vitro screening of antileishmanial compounds. | the development of new therapeutic leads against leishmaniasis relies primarily on screening of a large number of compounds on multiplication of clinically irrelevant transgenic promastigotes. the advent of the successful in vitro culture of axenic amastigotes allows the development of transgenic axenic amastigotes as a primary screen which can test compounds in a high throughput mode like promastigotes, still representative of the clinically relevant mammalian amastigotes stage. the present stu ... | 2012 | 22945482 |
| 2-alkynoic fatty acids inhibit topoisomerase ib from leishmania donovani. | 2-alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. in this work we synthesized the 2-octadecynoic acid (2-oda), 2-hexadecynoic acid (2-hda), and 2-tetradecynoic acid (2-tda) and show that 2-oda is the best inhibitor of the leishmania donovani dna topoisomerase ib enzyme (ldtopib) with an ec(50)=5.3±0.7μm. the potency of ldtopib inhibition follows the trend 2-oda>2-hda>2-tda, indicating that the e ... | 2012 | 22932312 |
| involvement of cd4⁺ foxp3⁺ regulatory t cells in persistence of leishmania donovani in the liver of alymphoplastic aly/aly mice. | visceral leishmaniasis (vl) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, leishmania donovani and l. infantum (l. chagasi). relapse of disease is frequent in immunocompromised patients, in which the number of vl cases has been increasing recently. the present study is aimed to improve the understanding of mechanisms of l. donovani persistence in immunocompromised conditions using alymphoplastic aly/aly mice. hepatic parasite burden, granuloma ... | 2012 | 22928057 |
| in vitro antileishmanial drug susceptibility of clinical isolates from patients with indian visceral leishmaniasis--status of newly introduced drugs. | regional variations in susceptibility of leishmania donovani clinical isolates have been reported to antimonials but not other antileishmanial drugs. therefore, we evaluated the susceptibility of four antileishmanial drugs in clinical use in 28 clinical isolates from endemic and non-endemic regions in the j774a.1 macrophage cell line, and we found increased tolerance of miltefosine and paromomycin in isolates from a patient from a high endemic region. effective dose for 90% killing (ed(90)) valu ... | 2012 | 22927497 |
| real-time pcr to quantify leishmania donovani in hamsters. | visceral leishmaniasis, a vector-borne disease caused by leishmania donovani and leishmania infantum , currently affects 12 million individuals in 88 countries. in the present study, a real-time pcr (rt-pcr) assay has been optimized and validated against 2 other routine methods, i.e., microscopy and limiting dilution culture assay, to estimate parasite load in the liver of infected syrian hamsters (mesocricetus auratus). a set of specific primers amplified a 116-bp target template of the kinetop ... | 2013 | 22924923 |
| il-10-producing th1 cells and disease progression are regulated by distinct cd11c⁺ cell populations during visceral leishmaniasis. | il-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of cd4⁺ ifnγ⁺ t cells committed to il-10 production. here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional cd11c(hi) dcs that produce both il-10 and il-27 are capable of inducing il-10-producing th1 cells in vi ... | 2012 | 22911108 |
| visceral leishmaniasis: a case report. | although leishmaniasis is widely prevalent in the eastern states of india namely bihar, jharkhand, uttar pradesh and west bengal, diagnosing the illness is still difficult. we present a case of a 20-year-old agricultural labourer with a history of recurrent fever, progressive weakness and abdominal discomfort associated with loss of appetite for six months followed by petechial hemorrhages over body.on examination there was hepato-splenomegaly. a diagnosis of visceral leishmaniasis (kala-azar) w ... | 2012 | 22905054 |
| pentacyclic ingamine alkaloids, a new antiplasmodial pharmacophore from the marine sponge petrosid ng5 sp5. | two new pentacyclic ingamine alkaloids, namely 22(s)-hydroxyingamine a (2) and dihydroingenamine d (3), together with the known ingamine a (1), have been isolated from marine sponge petrosid ng5 sp5 (family petrosiidae) obtained from the open repository of the national cancer institute, usa. the structures of compounds 1-3 were determined using 1d and 2d nmr, and hresims techniques. the absolute configuration of both the c9 and c22 of 2 was determined as (s) using a modified mosher esterificatio ... | 2012 | 22903383 |
| the role of nf-κb activation during protection against leishmania infection. | members of the nuclear factor-κb (nf-κb) family of transcription factors regulate a variety of molecules involved in host defense against pathogens. a prominent role of nf-κb in innate and adoptive immunity is based on the regulation of inducible transcription of various genes whose products are essential components of the immune response such as cytokines, chemokines, and adhesion molecules. since the discovery of the five members of the nf-κb transcription factor family, rela, c-rel, relb, p50 ... | 2012 | 22901377 |
| deletion of mitochondrial associated ubiquitin fold modifier protein ufm1 in leishmania donovani results in loss of β-oxidation of fatty acids and blocks cell division in the amastigote stage. | recently, we described the existence of the ubiquitin fold modifier 1 (ufm1) and its conjugation pathway in leishmania donovani. we demonstrated the conjugation of ufm1 to proteins such as mitochondrial trifunctional protein (mtp) that catalyses β-oxidation of fatty acids in l. donovani. to elucidate the biological roles of the ufm1-mediated modifications, we made an l. donovani ufm1 null mutant (ufm1(-/-)). loss of ufm1 and consequently absence of ufm1 conjugation with mtp resulted in diminishe ... | 2012 | 22897198 |
| the histone acetyl transferase ldhat1 from leishmania donovani is regulated by s-phase cell cycle kinase. | histone acetyl transferases (hats) are important histone modifiers that affect critical cellular processes like transcription, dna replication and repairs through highly dynamic chromatin remodelling. our earlier studies recognized ldhat1 as a substrate of the s-phase cell cycle kinase ldcyc1-crk3 from leishmania donovani. here, we confirm through site-directed mutagenesis that rxl-like cyclin-binding (cy) motif dependent interaction of ldhat1 with ldcyc1 is essential for its phosphorylation at ... | 2012 | 22889278 |
| post-kala-azar dermal leishmaniasis in visceral leishmaniasis-endemic communities in bihar, india. | we assessed the prevalence of post-kala-azar dermal leishmaniasis (pkdl), a late cutaneous manifestation of visceral leishmaniasis (vl), in 16 vl-endemic communities in bihar, india. the prevalence of confirmed pkdl cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. the clinical history and treatment of the post-kala-azar dermal leishmaniasis cases are discussed. | 2012 | 22882665 |
| pcr-based detection of leishmania donovani dna in a stray dog from a visceral leishmaniasis endemic focus in bangladesh. | although phlebotomus argentipes as the only known vector of visceral leishmaniasis (vl) is zoophilic in nature, vl is considered to be anthroponotic in the indian subcontinent. peripheral blood samples from 85 stray dogs were examined for any molecular evidence of leishmania infection in vl endemic areas of bangladesh. parasite dna was detected in a blood sample from 1 of 85 (1.2%) stray dogs using its1-pcr, and pcr sequencing of the rrna-its and cytochrome b gene confirmed that the parasitic dn ... | 2013 | 22878541 |
| development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis. | the purpose of this study was to explore the applicability, targeting potential and drug delivery to specialized phagocytes via phosphatidylserine (ps)-specific ligand-anchored nanocapsules (ncs) bearing doxorubicin. | 2012 | 22872448 |
| immunization with leishmania vaccine-alum-bcg and montanide isa 720 adjuvants induces low-grade type 2 cytokines and high levels of igg2 subclass antibodies in the vervet monkey (chlorocebus aethiops) model. | the availability of hundreds of adjuvants has prompted a need for identifying rational standards for the selection of adjuvant formulation based on sound immunological principles for human vaccines. as cytokines elaborated by activated t cells are required for the regulation of isotype switch during b-cell development, a study of th2 cytokines and subclass distribution of the antibodies may shed new light on the processes involved in the polarization of the immune responses during vaccination st ... | 2012 | 22862788 |
| sialoglycosylation of rbc in visceral leishmaniasis leads to enhanced oxidative stress, calpain-induced fragmentation of spectrin and hemolysis. | visceral leishmaniasis (vl) caused by the intracellular parasite leishmania donovani accounts for an estimated 12 million cases of human infection. it is almost always associated with anemia, which severely complicates the disease course. however, the pathological processes leading to anemia in vl have thus far not been adequately characterized to date. in studying the glycosylation patterns of peripheral blood cells we found that the red blood cells (rbc) of vl patients (rbc(vl)) express eight ... | 2012 | 22860118 |
| manadoperoxides, a new class of potent antitrypanosomal agents of marine origin. | chemical investigation of the marine sponge plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides b-k (3-5 and 7-13) and peroxyplakoric esters b(3) (6) and c (14). eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing thf-type ring in the side chain. the library of endoperoxide derivatives was evaluated for in vitro activity against trypanosoma brucei rhodesiense and leishmania donovani. some compounds, such as manadopero ... | 2012 | 22859016 |
| quantitative proteomic profiling of the promastigotes and the intracellular amastigotes of leishmania donovani isolates identifies novel proteins having a role in leishmania differentiation and intracellular survival. | protozoan parasites of the genus leishmania are important human pathogens that cycle between an extracellular promastigote stage residing in the sandflies and an intracellular amastigote stage colonizing the phagolysosomal compartment of the mammalian macrophages. here, we used the isobaric tagging method to quantify the global proteomic differences between the promastigotes and the intracellular amastigotes of three different leishmania donovani clones derived from the thp-1 human macrophage ce ... | 2012 | 22850196 |
| exploring the biological activities of echeveria leucotricha. | echeveria leucotricha j. a. purpus (crassulaceae) was evaluated for its potential antibacterial, antifungal, antiparasitic, cytotoxic and anti-inflammatory bioactivities. aerial parts were extracted with hexane, methanol and chloroform, and fractionated accordingly. biological activity was assessed in vitro against five gram-positive and four gram-negative bacteria, four human pathogenic fungi and the protozoan leishmania donovani. extracts and fractions showing bioactivities were further invest ... | 2013 | 22845689 |
| deletion of an atp-binding cassette protein subfamily c transporter in leishmania donovani results in increased virulence. | genome comparison of leishmania species sequenced to date has identified several hundred differentially distributed genes which are present as functional genes in some species but as pseudogenes or absent in others. it is not clear whether these differentially distributed genes are important for disease, redundant or even harmful for a particular leishmania species though a few of these genes have been implicated in leishmania infection tissue tropism. the l. infantum linj.24.1510 gene is an atp ... | 2012 | 22841683 |
| analysis of sequence, structure of gapdh of leishmania donovani and its interactions. | drug resistance acquired by leishmania donovani (ldv) is a major problem in the treatment and control of visceral leishmaniasis (vl). glyceraldehyde-3-phosphate dehydrogenase (gapdh), a major glycolytic enzyme has been targeted as is found in other protozoan which cause diseases like sleeping sickness. gapdh gene of ldv (ag83 strain) was amplified, sequenced, and modeled on the basis of crystal structure of leishmania mexicana. the model of the ldv gapdh exhibited nad-binding domain with rossman ... | 2013 | 22830998 |
| pcr-based detection of leishmania dna in skin samples of post kala-azar dermal leishmaniasis patients from an endemic area of bangladesh. | post kala-azar dermal leishmaniasis (pkdl) is a sequel of visceral leishmaniasis (vl) and pkdl patients are an important reservoir for anthroponotic transmission of vl. therefore, diagnosis and treatment of pkdl is important for the kala-azar elimination program in south asia, including bangladesh. while definitive diagnosis of pkdl is still based on microscopy, despite the low sensitivity of this method of diagnosis, pcr for identification of kinetoplast dna (kdna) from leishmania parasites is ... | 2012 | 22814154 |
| phylogenic analysis of chinese leishmania isolates based on small subunit ribosomal rna (ssu rrna) and 7 spliced leader rna (7sl rna). | the leishmaniases are zoonotic diseases caused by protozoan parasites of the genus leishmania. leishmaniases are still endemic in china, especially in the west and northwest froniter regions. to revalue the preliminary phylogenetic results of chinese leishmania isolates, we amplified partial fragment of small subunit ribosomal rna (ssu rrna) and 7 spliced leader rna (7sl rna), then tested the phylogenetic relationships among chinese leishmania isolates and their relatives by analyzing ssu rrna g ... | 2012 | 22807046 |
| mycobacterium indicus pranii (mw) re-establishes host protective immune response in leishmania donovani infected macrophages: critical role of il-12. | leishmania donovani, a protozoan parasite, causes a strong immunosuppression in a susceptible host and inflicts the fatal disease visceral leishmaniasis. relatively high toxicity, low therapeutic index, and failure in reinstating host-protective anti-leishmanial immune responses have made anti-leishmanial drugs patient non-compliant and an immuno-modulatory treatment a necessity. therefore, we have tested the anti-leishmanial efficacy of a combination of a novel immunomodulator, mycobacterium in ... | 2012 | 22792256 |
| role of oxidative stress and apoptosis in the cellular response of murine macrophages upon leishmania infection. | leishmania parasites are able to survive in the macrophage, one of the most hostile environments of the vertebrate host. the present study investigated how leishmania infection influences these host cell defence mechanisms. macrophages were infected with antimony-susceptible and -resistant leishmania strains. free radical production in leishmania-infected macrophages was measured by electron paramagnetic resonance. apoptosis was detected with fluorescence microscopy using annexin-v fitc labellin ... | 2012 | 22776404 |
| evaluation of antileishmanial activity of south indian medicinal plants against leishmania donovani. | infections due to protozoa of the genus leishmania are a major worldwide health problem, with high endemicity in developing countries. the aim of this study was to evaluate the in vitro antileishmanial activity of the acetone and methanol leaf extracts of anisomeles malabarica, flower of gloriosa superba, leaf of ocimum basilicum, leaf and seed of ricinus communis against promastigotes form of leishmania donovani. antiparasitic evaluations of different plant crude extracts were performed on 96 w ... | 2012 | 22771864 |
| animal reservoirs of visceral leishmaniasis in india. | visceral leishmaniasis (vl) is a disease that has both zoonotic and anthroponotic etiologies. in india, vl is endemic, considered to be anthroponotic, and caused by leishmania donovani . anthroponotic diseases are maintained by transmission from human to human and to a lesser extent from human to animals. serum samples from 1,220 animals from 7 human vl endemic districts of bihar, india, were tested for antibodies to a recombinant kinetoplast antigen (rk39 antigen) present in amastigotes of visc ... | 2013 | 22765517 |
| combination of paromomycin and miltefosine promotes tlr4-dependent induction of antileishmanial immune response in vitro. | to evaluate the in vitro activity of antileishmanial drugs, paromomycin and miltefosine, to generate th-1-biased immunomodulation in hosts against intracellular leishmania donovani. | 2012 | 22761329 |
| genetic markers for ssg resistance in leishmania donovani and ssg treatment failure in visceral leishmaniasis patients of the indian subcontinent. | the current standard to assess pentavalent antimonial (ssg) susceptibility of leishmania is a laborious in vitro assay of which the result has little clinical value because ssg-resistant parasites are also found in ssg-cured patients. candidate genetic markers for clinically relevant ssg-resistant parasites identified by full genome sequencing were here validated on a larger set of clinical strains. we show that 3 genomic locations suffice to specifically detect the ssg-resistant parasites found ... | 2012 | 22753945 |
| genetic typing reveals monomorphism between antimony sensitive and resistant leishmania donovani isolates from visceral leishmaniasis or post kala-azar dermal leishmaniasis cases in india. | resistance to pentavalent antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (vl), also known as kala-azar (ka), caused by leishmania donovani. in india, over 60% of ka patients are unresponsive to the first-line drug sodium antimony gluconate (sag). resistance determinants in laboratory strains are partly known; however, the mechanism operating in field isolates is not well understood. in this study, we attempted to analyze the genetic polymorphism ... | 2012 | 22752721 |
| leishmania donovani pteridine reductase 1: comparative protein modeling and protein-ligand interaction studies of the leishmanicidal constituents isolated from the fruits of piper longum. | visceral leishmaniasis or kala-azar is caused by the dimorphic parasite leishmania donovani in the indian subcontinent. treatment options for kala-azar are currently inadequate due to various limitations. currently, drug discovery for leishmaniases is oriented towards rational drug design; the aim is to identify specific inhibitors that target particular metabolic activities as a possible means of controlling the parasites without affecting the host. leishmania salvages pteridin from its host an ... | 2012 | 22752544 |
| evidence for involvement of th17 type responses in post kala azar dermal leishmaniasis (pkdl). | post kala-azar dermal leishmaniasis (pkdl), a dermal sequel of visceral leishmaniasis, caused by leishmania donovani, constitutes an important reservoir for the parasite. parallel functioning of counter acting immune responses (th1/th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis. | 2012 | 22724038 |
| an image-based high-content screening assay for compounds targeting intracellular leishmania donovani amastigotes in human macrophages. | leishmaniasis is a tropical disease threatening 350 million people from endemic regions. the available drugs for treatment are inadequate, with limitations such as serious side effects, parasite resistance or high cost. driven by this need for new drugs, we developed a high-content, high-throughput image-based screening assay targeting the intracellular amastigote stage of different species of leishmania in infected human macrophages. the in vitro infection protocol was adapted to a 384-well-pla ... | 2012 | 22720099 |
| an antileishmanial prenyloxy-naphthoquinone from roots of plumbago zeylanica. | leishmania donovani, an obligate intracellular parasite of genus leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the indian subcontinent and east africa. generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use. this study discloses strong in vitro antileishmanial activity of 2-methyl-5 -(3'-methyl ... | 2013 | 22708724 |
| antifungal depsidone metabolites from cordyceps dipterigena, an endophytic fungus antagonistic to the phytopathogen gibberella fujikuroi. | among thirty four endophytic fungal strains screened for in vitro antagonism, the endophytic fungus cordyceps dipterigena was found to strongly inhibit mycelial growth of the plant pathogenic fungus gibberella fujikuroi. two new depsidone metabolites, cordycepsidone a (1) and cordycepsidone b (2), were isolated from the pda culture extract of c. dipterigena and identified as being responsible for the antifungal activity. elucidation of their chemical structures was carried out using 1d and 2d nm ... | 2012 | 22707798 |
| intracellular pathogen leishmania donovani activates hypoxia inducible factor-1 by dual mechanism for survival advantage within macrophage. | recent evidence established a crucial role for mammalian oxygen sensing transcription factor hypoxia inducible factor-1 (hif-1) in innate immunity against intracellular pathogens. in response to most of these pathogens host phagocytes increase transcription of hif-1α, the regulatory component of hif-1 to express various effector molecules against invaders. leishmania donovani (ld), a protozoan parasite and the causative agent of fatal visceral leishmaniasis resides in macrophages within mammalia ... | 2012 | 22701652 |
| mechanistic insights into the dual inhibition strategy for checking leishmaniasis. | leishmaniasis (1) is an endemic disease mainly caused by the protozoan leishmania donovani (ld). polyamines have been identified as essential organic compounds for the growth and survival of ld. these are synthesized in ld by polyamine synthesis pathway comprising of many enzymes such as ornithine decarboxylase (odc), spermidine synthase (ss), and s-adenosylmethionine decarboxylase. inhibition of these enzymes in ld offers a viable prospect to check its growth and development. in the present wor ... | 2012 | 22694167 |
| synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine k for antimalarial, antileishmanial, antibacterial, antifungal and anti-hiv activities. | fifty analogues of batzelladine k were synthesized and evaluated for in vitro antimalarial (plasmodium falciparum), antileishmanial (leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (hiv-1) activities. analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive d6 strain with ic50 1.25 and 0.88 μm and chloroquine-resistant w2 strain with ic50 1.64 and 1.07 μm, respectively. analogues 12c and 14c having nonyl substitution showed the mo ... | 2012 | 26404724 |
| involvement of the leishmania donovani virulence factor a2 in protection against heat and oxidative stress. | leishmania is an obligate intracellular protozoan parasite that infects cells of the reticulo-endothelial system. host defences against leishmania include fever and oxidant production, and the parasite has developed a number of defence mechanisms to neutralize the host response. the leishmania donovani a2 family of proteins has been shown to be essential for survival in mammalian visceral organs. here we provide evidence that a2 proteins protect the parasite against host defences, namely heat st ... | 2012 | 22691540 |
| leishmania donovani exploits host deubiquitinating enzyme a20, a negative regulator of tlr signaling, to subvert host immune response. | tlrs, which form an interface between mammalian host and microbe, play a key role in pathogen recognition and initiation of proinflammatory response thus stimulating antimicrobial activity and host survival. however, certain intracellular pathogens such as leishmania can successfully manipulate the tlr signaling, thus hijacking the defensive strategies of the host. despite the presence of lipophosphoglycan, a tlr2 ligand capable of eliciting host-defensive cytokine response, on the surface of le ... | 2012 | 22685311 |
| a leishmaniasis study: structure-based screening and molecular dynamics mechanistic analysis for discovering potent inhibitors of spermidine synthase. | protozoa leishmania donovani (ld) is the main cause of the endemic disease leishmaniasis. spermidine synthase (ss), an important enzyme in the synthetic pathway of polyamines in ld, is an essential element for the survival of this protozoan. targeting ss may provide an important aid for the development of drugs against ld. however, absence of tertiary structure of spermidine synthase of leishmania donovani (lss) limits the possibilities of structure based drug designing. presence of the same enz ... | 2012 | 22684087 |
| aubr(3) mediated glycosidations: synthesis of tetrasaccharide motif of the leishmania donovani lipophosphoglycan. | tetrasaccharide cap present in lipophosphoglycan of the leishmania donovani responsible for visceral leishmaniaisis is synthesized as a fully protected propargyl glycoside. aubr(3) mediated selective glycosylation of propargyl 1,2-orthoester in the presence of propargyl glycoside is employed as a key step to obtain propargyl containing oligomers. further, propargyl tetrasaccharide is connected with a long chain hydrocarbon containing azidothiol functionality situated at two terminal ends via 'cl ... | 2012 | 22660966 |
| drug susceptibility in leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. | with widespread resistance to antimonials in visceral leishmaniasis (vl) in the indian subcontinent, miltefosine (mil) has been introduced as the first line therapy. surveillance of mil susceptibility in natural populations of leishmania donovani is vital to preserve it and support the vl elimination program. | 2012 | 22629478 |
| tlr-mediated distinct ifn-γ/il-10 pattern induces protective immunity against murine visceral leishmaniasis. | resistance to murine visceral leishmaniasis (vl) correlates with the development of an ifn-γ predominant immune response. beta1,4-galactose terminal glycans are potent inducers of ifn-γ. here, we demonstrate the efficacy of a 29 kda β1,4-galactose terminal glycoprotein (gp29) of leishmania donovani (ld) in an in vitro macrophage model and an in vivo mouse model of vl. gp29 induced splenic macrophages to release no and ros in appreciable amounts that resulted in effective parasite clearance from ... | 2012 | 22622993 |
| coinfection of leptomonas seymouri and leishmania donovani in indian leishmaniasis. | leishmania donovani is considered the causative organism of visceral leishmaniasis (vl) and post-kala-azar dermal leishmaniasis (pkdl). testing of 4/29 dna samples from vl and pkdl patients as well as 2/7 field isolates showed an aberrant internal transcribed spacer 1 (its1) restriction fragment length polymorphism (rflp) pattern, which upon sequencing strongly matched leptomonas seymouri, thus confirming its presence in indian leishmaniasis. | 2012 | 22622439 |
| defeating leishmania resistance to miltefosine (hexadecylphosphocholine) by peptide-mediated drug smuggling: a proof of mechanism for trypanosomatid chemotherapy. | miltefosine (hexadecylphosphocholine, hepc), the first orally active drug successful against leishmaniasis, is especially active on the visceral form of the disease. resistance mechanisms are almost exclusively associated to dysfunction in hepc uptake systems. in order to evade the requirements of its cognate receptor/translocator, hepc-resistant leishmania donovani parasites (r40 strain) were challenged with constructs consisting of an ω-thiol-functionalized hepc analogue conjugated to the cell ... | 2012 | 22609351 |
| discovery of a new antileishmanial hit in 8-nitroquinoline series. | a series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward leishmania donovani promastigotes. in parallel, the in vitro cytotoxicity of these molecules was assessed on the murine j774 and human hepg2 cell lines. thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an ic(50) value of 6.6 μm and cc(50) values ≥ 100 μm, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference ( ... | 2012 | 22608675 |
| synthesis and anti-leishmanial activity of 1-aryl-β-carboline derivatives against leishmania donovani. | β-carbolines from various natural and synthetic sources have been known to show diverse biological activities. as a part of our current ongoing project to search for potent natural product-derived anti-leishmanial compounds, we have synthesized a series of substituted 1-aryl-β-carboline derivatives. a total of 22 compounds were synthesized and tested in vitro against leishmania donovani, out of which 6 compounds (4, 5, 10, 11, 19 and 22) showed notably more activity than the standard miltefosine ... | 2012 | 22608390 |
| glycyrrhizic acid suppresses cox-2-mediated anti-inflammatory responses during leishmania donovani infection. | the aim of the present study was to characterize glycyrrhizic acid (ga) and assess its immunomodulatory potential in a model of experimental visceral leishmaniasis. | 2012 | 22589456 |
| successful therapeutic splenectomy in an hiv patient with relapsing visceral leishmaniasis. | a 43-year-old hiv-positive ethiopian immigrant presented with persistent diarrhoea, hepatosplenomegaly and pancytopaenia. visceral leishmaniasis was diagnosed by multiple gastrointestinal tract biopsies. blood polymerase chain reaction (pcr) was positive for leishmania donovani. despite highly active antiretroviral therapy (haart) and multiple courses of antileishmanial treatments, including liposomal amphotericin and sodium stibogluconate, the patient had multiple relapses. cd4 counts remained ... | 2012 | 22581957 |
| leishmania donovani: cd2 biased immune response skews the sag mediated therapy for a predominant th1 response in experimental infection. | we have evaluated the effect of combining cd2 with conventional antimonial (sb) therapy in protection in balb/c mice infected with either drug sensitive or resistant strain of leishmania donovani with 3×10(7) parasites via-intra-cardiac route. mice were treated with anti cd2 adjunct sag sub-cutaneously twice a week for 4 weeks. assessment for measurement of weight, spleen size, anti-leishmania antibody titer, t cell and anti-leishmanial macrophage function was carried out day 0, 10, 22 and 34 po ... | 2012 | 22580024 |
| leishmania donovani recombinant iron superoxide dismutase b1 protein in the presence of tlr-based adjuvants induces partial protection of balb/c mice against leishmania major infection. | in this study, we tested the protective efficacy of recombinant leishmania donovani iron superoxide dismutase b1 (sodb1) against leishmania major infection in balb/c mice. mice were challenged with l. major 3weeks after the second boost immunization with rsodb1 alone or in the presence of adjuvants. injection of balb/c mice with rsodb1 alone elicited both humoral and cellular immune responses. administration of rsodb1 with cpg odn or gla-se (a synthetic toll-like receptor 4 agonist) adjuvant res ... | 2012 | 22580023 |
| leishmanicidal compounds from the fruits of piper longum. | one new alkaloid amide, piperlongumide (1) [n-isobutyl-19-(3',4'-methylenedioxyphenyl)-2e,4e nonadecadienamide], and six known compounds with leishmanicidal activity against promastigotes and axenic amastigotes of leishmania donovani were isolated from the n-hexane fraction of the fruits of piper longum. the structure of 1 was elucidated by spectroscopic evidences. | 2012 | 22576441 |
| a highly basic sequence at the n-terminal region is essential for targeting the dna replication protein orc1 to the nucleus in leishmania donovani. | the conserved eukaryotic dna replication protein orc1 is one of the constituents of pre-replication complexes that assemble at or very near origins prior to replication initiation. orc1 has been shown to be constitutively nuclear in leishmania major. this study investigates the sequences involved in nuclear localization of orc1 in leishmania donovani, the causative agent of visceral leishmaniasis. nuclear localization signals (nlss) have been reported in only a few leishmania proteins. functiona ... | 2012 | 22575896 |
| evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. | most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. an antineoplastic drug, cisplatin (cis-diamminedichloroplatinum ii; cddp), is recognized as a dna-damaging drug which also induces alteration of cell- ... | 2012 | 22563510 |
| comparison of electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization for a lipidomic analysis of leishmania donovani. | a comparison of electrospray ionization (esi), atmospheric pressure chemical ionization (apci) and atmospheric pressure photoionization (appi) for the analysis of a wide range of lipids has been performed on standard mixtures and extracts of leishmania donovani promastigotes resistant to amphotericin b (amb). calibration model, precision, limits of detection and quantification (lod and loq) were assessed for each source. appi provided the highest signal, signal-to-noise (s/n), and sensitivity fo ... | 2012 | 22560453 |
| novel 3-nitro-1h-1,2,4-triazole-based amides and sulfonamides as potential antitrypanosomal agents. | a series of novel 3-nitro-1h-1,2,4-triazole-based (and in some cases 2-nitro-1h-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. out of 36 compounds tested, 29 (mostly 3-nitro-1h-1,2,4-triazoles) displayed significant activity against trypanosoma cruzi intracellular amastigotes (ic(50) ranging from 28 nm to 3.72 μm) without concomitant toxicity to l6 host cells (selectivity 66-2782). twen ... | 2012 | 22550999 |
| selective inhibitors of protozoan protein n-myristoyltransferases as starting points for tropical disease medicinal chemistry programs. | inhibition of n-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. in order to identify inhibitors of protozoan nmts, we chose to screen a diverse subset of the pfizer corporate collection against plasmodium falciparum and leishmania donovani nmts. primary screening hits against either enzyme were tested for selectivity over both human nmt isoforms (hs1 and hs2) and for broad-spectrum anti- ... | 2012 | 22545171 |
| enhanced leishmanicidal activity of cryptopeptide chimeras from the active n1 domain of bovine lactoferrin. | two antimicrobial cryptopeptides from the n1 domain of bovine lactoferrin, lactoferricin (lfcin17-30) and lactoferrampin (lfampin265-284), together with a hybrid version (lfchimera), were tested against the protozoan parasite leishmania. all peptides were leishmanicidal against leishmania donovani promastigotes, and lfchimera showed a significantly higher activity over its two composing moieties. besides, it was the only peptide active on leishmania pifanoi axenic amastigotes, already showing ac ... | 2012 | 22543751 |
| evaluation of leishmania donovani protein disulfide isomerase as a potential immunogenic protein/vaccine candidate against visceral leishmaniasis. | in leishmania species, protein disulfide isomerase (pdi)--a redox chaperone, is reported to be involved in its virulence and survival. this protein has also been identified, through proteomics, as a th1 stimulatory protein in the soluble lysate of a clinical isolate of leishmania donovani (ldpdi). in the present study, the molecular characterization of ldpdi was carried out and the immunogenicity of recombinant ldpdi (rldpdi) was assessed by lymphocyte proliferation assay (ltt), nitric oxide (no ... | 2012 | 22539989 |
| a proteogenomic approach to map the proteome of an unsequenced pathogen - leishmania donovani. | visceral leishmaniasis or kala azar is the most severe form of leishmaniasis and is caused by the protozoan parasite leishmania donovani. there is no published report on l. donovani genome sequence available till date, although the genome sequences of three related leishmania species are already available. thus, we took a proteogenomic approach to identify proteins from two different life stages of l. donovani. from our analysis of the promastigote (insect) and amastigote (human) stages of l. do ... | 2012 | 22539434 |
| antiprotozoal and antimicrobial compounds from the plant pathogen septoria pistaciarum. | four new 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids, 17-hydroxy-n-(o-methyl)septoriamycin a (1), 17-acetoxy-n-(o-methyl)septoriamycin a (2), 13-(s)-hydroxy-n-(o-methyl)septoriamycin a (3), and 13-(r)-hydroxy-n-(o-methyl)septoriamycin a (4), together with the known compounds (+)-cercosporin (5), (+)-14-o-acetylcercosporin (6), (+)-di-o-acetylcercosporin (7), lumichrome, and brassicasterol, were isolated from an ethyl acetate extract of a culture medium of septoria pistaciarum. methylation of s ... | 2012 | 22530813 |
| leishmania-induced biphasic ceramide generation in macrophages is crucial for uptake and survival of the parasite. | the initial macrophage-leishmania donovani interaction results in the formation of membrane platforms, termed lipid rafts, that help in the entry of the parasite. therefore, it is imperative that the parasite designs a strategy to modulate its uptake and survival within the macrophages. herein, we report leishmania-triggered biphasic ceramide generation. in the first phase, l. donovani promastigotes induce activation of acid sphingomyelinase (asmase), which catalyzes the formation of ceramide fr ... | 2012 | 22517914 |
| the efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin b in rodent models of leishmaniasis and pulmonary aspergillosis infection. | amphotericin b (amb) is used to treat both fungal and leishmanial infections, which are of major significance to human health. clinical use of free amb is limited by its nephrotoxicity, whereas liposomal amb is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. in this study we analysed the potential of non-ionic surfactant vesicles (niv) given by nebulisation ... | 2012 | 22516093 |
| a morphologically distinct phlebotomus argentipes population from active cutaneous leishmaniasis foci in central sri lanka. | although the reported aetiological agent of cutaneous leishmaniasis (cl) in sri lanka is leishmania donovani, the sandfly vector remains unknown. ninety-five sandflies, 60 females and 35 males, collected in six localities in the district of matale, central sri lanka, close to current active transmission foci of cl were examined for taxonomically relevant characteristics. eleven diagnostic morphological characters for female sandflies were compared with measurements described for indian and sri l ... | 2012 | 22510837 |
| a novel recombinant leishmania donovani p45, a partial coding region of methionine aminopeptidase, generates protective immunity by inducing a th1 stimulatory response against experimental visceral leishmaniasis. | the development of a vaccine against visceral leishmaniasis (vl) conferring long-lasting immunity remains a challenge. identification and proteomic characterization of parasite proteins led to the detection of p45, a member of the methionine aminopeptidase family. to our knowledge the present study is the first known report that describes the molecular and immunological characterization of p45. recombinant leishmania donovani p45 (rldp45) induced cellular responses in cured hamsters and generate ... | 2012 | 22502587 |
| overexpression of s4d mutant of leishmania donovani adf/cofilin impairs flagellum assembly by affecting actin dynamics. | leishmania, like other eukaryotes, contains large amounts of actin and a number of actin-related and actin binding proteins. our earlier studies have shown that deletion of the gene corresponding to leishmania actin-depolymerizing protein (adf/cofilin) adversely affects flagellum assembly, intracellular trafficking, and cell division. to further analyze this, we have now created adf/cofilin site-specific point mutants and then examined (i) the actin-depolymerizing, g-actin binding, and actin-bou ... | 2012 | 22492507 |
| identification and characterization of a novel leishmania donovani antigen for serodiagnosis of visceral leishmaniasis. | despite several drawbacks, rk39-based rapid immunochromatographic test is widely used for the diagnosis of visceral leishmaniasis (vl) in the indian subcontinent. there is an urgent need to develop a better antigen. in this study we separated crude soluble antigens of leishmania donovani by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and hybridized with pool sera from pre- and post-treated vl patients, 6 months follow-up, endemic healthy (ehc), and nonendemic healthy controls (nehc ... | 2012 | 22492143 |
| amino acid, dipeptide and pseudodipeptide conjugates of ring-substituted 8-aminoquinolines: synthesis and evaluation of anti-infective, β-haematin inhibition and cytotoxic activities. | three new series of 8-aminoquinolines with modifications in the side-chain by conjugation with amino acids, dipeptides and pseudodipeptides have been synthesized. the synthesized compounds were tested for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant plasmodium falciparum strains, in vitro cytotoxicity in mammalian kidney cells (vero), in vitro antileishmanial activity against leishmania donovani, in vitro antimicrobial activity and in vitro inhibition of ... | 2012 | 22483965 |
| b cell: t cell interactions occur within hepatic granulomas during experimental visceral leishmaniasis. | hepatic resistance to leishmania donovani infection in mice is associated with the development of granulomas, in which a variety of lymphoid and non-lymphoid populations accumulate. although previous studies have identified b cells in hepatic granulomas and functional studies in b cell-deficient mice have suggested a role for b cells in the control of experimental visceral leishmaniasis, little is known about the behaviour of b cells in the granuloma microenvironment. here, we first compared the ... | 2012 | 22479545 |
| synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives. | a new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against leishmania donovani and trypanosoma brucei brucei. results from these structure-activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against l. donovani promastigotes and amastigotes parasites (ic(50) values in a range of 2-11 μm). additionally, compound 3b has emerged from this study as the most active compound in the serie ... | 2012 | 22472166 |
| terpenoidal constituents of eucalyptus loxophleba ssp. lissophloia. | eucalyptus has been a source of a number of biologically active compounds. the anti-leishmanial activity of terpenoids from eucalyptus loxophleba (benth.) ssp. lissophloia (myrtaceae) has not yet been investigated. | 2012 | 22468852 |
| invariant nkt cells drive hepatic cytokinic microenvironment favoring efficient granuloma formation and early control of leishmania donovani infection. | the development of inflammatory granulomas around infected kupffer cells is necessary for hepatic parasite clearance during visceral leishmaniasis. invariant nkt (inkt) cells are predominant t cells in the mouse liver and can synthesize large quantities of il-4 and ifn-γ, two cytokines involved in granuloma formation. this study analyzed the role of inkt cells in the hepatic immune response during leishmania donovani infection, using a murine model of wild-type (wt) and inkt cell-deficient (jα18 ... | 2012 | 22457760 |
| peroxisome proliferator-activated receptor-γ-mediated polarization of macrophages in leishmania infection. | infection is the outcome of a contest between a pathogen and its host. in the disease leishmaniasis, the causative protozoan parasites are harbored inside the macrophages. leishmania species adapt strategies to make the infection chronic, keeping a balance between their own and the host's defense so as to establish an environment that is favorable for survival and propagation. activation of peroxisome proliferator-activated receptor (ppar) is one of the tactics used. this ligand-activated nuclea ... | 2012 | 22448168 |
| 115 kda serine protease confers sustained protection to visceral leishmaniasis caused by leishmania donovani via ifn-γ induced down-regulation of tnf-α mediated mmp-9 activity. | visceral leishmaniasis caused by the intracellular parasite leishmania donovani is a major public health problem in the developing world. the emergence of increasing number of l. donovani strains resistance to antimonial drugs recommended worldwide requires the intervention of effective vaccine strategy for treatment of vl. in the present study l. donovani culture derived, soluble, secretory serine protease (psp) has been shown to be vaccine target of vl. protection from vl could be achieved by ... | 2013 | 22440312 |
| therapeutic immunization with radio-attenuated leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis. | after our promising results from prophylactic and therapeutic study (i.p. route) with the radio-attenuated leishmania donovani parasites against experimental murine visceral leishmaniasis, we prompted to check their therapeutic efficacy through i.m route. balb/c mice were infected with highly virulent l. donovani parasites. after 75 days, mice were treated with gamma (γ)-irradiated parasites. a second therapeutic immunization was given after 15 days of first immunization. the protection against ... | 2012 | 22437790 |
| marginal zone b cells regulate antigen-specific t cell responses during infection. | marginal zone b cells (mzb) participate in the early immune response to several pathogens. in this study, we show that in μmt mice infected with leishmania donovani, cd8 t cells displayed a greater cytotoxic potential and generated more effector memory cells compared with infected wild type mice. the frequency of parasite-specific, ifn-γ(+) cd4 t cells was also increased in μmt mice. b cells were able to capture parasites, which was associated with upregulation of surface igm and myd88-dependent ... | 2012 | 22412197 |
| differential peptide binding to cd40 evokes counteractive responses. | the antigen-presenting cell–expressed cd40 is implied in the regulation of counteractive immune responses such as induction of pro-inflammatory and anti-inflammatory cytokines interleukin (il)–12 and il-10, respectively. the mechanism of this duality in cd40 function remains unknown. here, we investigated whether such duality depends on ligand binding. based on cd40 binding, we identifed two dodecameric peptides, peptide-7 and peptide-19, from the phage peptide library. peptide-7 induces il-10 a ... | 2012 | 22406255 |
| preparation and antiprotozoal evaluation of promising β-carboline alkaloids. | the synthesis of β-carbolines and their in vitro antiplasmodial and antileishmanial activities were described herein. these molecules have also been studied concerning their in vitro cytotoxicity toward the human cell line thp1, in order to calculate their respective selectivity indexes (si). among the 20 tested molecules, four exhibited significant antiplasmodial activity on the w2 multi-resistant plasmodium falciparum strain (0.7 < ic₅₀ < 1.7 μm), in comparison with two references drugs (chlor ... | 2012 | 22397756 |
| molecular docking and in vitro antileishmanial evaluation of chromene-2-thione analogues. | leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. thus, development of new drugs against leishmania is an open area of investigation for synthetic organic chemists. to meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (tryr) enzyme required for redox balance of the parasite. these were screened on promastigote, axenic amastigote, and i ... | 2012 | 24936236 |
| augmentation of antileishmanial efficacy of miltefosine in combination with tuftsin against experimental visceral leishmaniasis. | current drugs for the treatment of visceral leishmaniasis are inadequate, and their efficacies are also compromised due to suppression of immune function during the course of infection. miltefosine is the only promising orally active antileishmanial drug, but due to its long half-life, there is risk of development of resistance. to overcome these problems, efforts are needed to develop combination therapy of miltefosine with effective immunostimulating agents where a decrease of parasitic burden ... | 2012 | 22392136 |
| regulation and spatial organization of pcna in trypanosoma brucei. | as in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite trypanosoma brucei. only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. we characterized the proliferating cell nuclear antigen in t. brucei (tbpcna) to establish a spatial and temporal marker for replication. interestingly, pcna distribution and regulat ... | 2012 | 22387477 |
| safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with leishmania donovani sonicate antigen delivered with adjuvants. | in this study, we report on the safety and skin delayed-type hypersensitivity (dth), responses of the leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-bcg (albcg), montanide isa 720 (misa) or monophosphoryl lipid a (mpla) in groups of vervet monkeys. following three intradermal injections of the inoculums on days 0, 28 and 42, safety and dth responses were assessed. preliminary tumor necrosis factor alpha (tnf-α) and interferon gamma (ifn-γ) levels were also mea ... | 2012 | 22370752 |
| genetic dissection of pyrimidine biosynthesis and salvage in leishmania donovani. | protozoan parasites of the leishmania genus express the metabolic machinery to synthesize pyrimidine nucleotides via both de novo and salvage pathways. to evaluate the relative contributions of pyrimidine biosynthesis and salvage to pyrimidine homeostasis in both life cycle stages of leishmania donovani, individual mutant lines deficient in either carbamoyl phosphate synthetase (cps), the first enzyme in pyrimidine biosynthesis, uracil phosphoribosyltransferase (uprt), a salvage enzyme, or both ... | 2012 | 22367196 |
| miltefosine triggers a strong proinflammatory cytokine response during visceral leishmaniasis: role of tlr4 and tlr9. | visceral leishmaniasis (vl) caused by the protozoan parasite, leishmania donovani, is associated with irregular fever, weight loss, hepatosplenomegaly and anemia. the therapeutic arsenal against vl is limited and the recent advent of a novel immunomodulatory drug, miltefosine has shown promising results for effective treatment of vl but its dependence on toll like receptors (tlr) has not been explored. in this study, we have shown that the non-cytotoxic dose (5 μm) of miltefosine could render si ... | 2012 | 22361489 |
| synthesis, biological evaluation, and structure-activity relationships of n-benzoyl-2-hydroxybenzamides as agents active against p. falciparum (k1 strain), trypanosomes, and leishmania. | in our efforts to identify novel chemical scaffolds for the development of new antiprotozoal drugs, a compound library was screened against toxoplasma gondii tachyzoites with activity discovered for n-(4-ethylbenzoyl)-2-hydroxybenzamide 1a against t. gondii as described elsewhere. synthesis of a compound set was guided by t. gondii sar with 1r found to be superior for t. gondii , also active against thai and sierra leone strains of plasmodium falciparum , and with superior admet properties as de ... | 2012 | 22352841 |
| leishmania donovani mitochondrial iron superoxide dismutase a is released into the cytosol during miltefosine induced programmed cell death. | the oxidative phosphorylation process is the main source of endogenous reactive oxygen species (ros) such as superoxide in mitochondria. in mammals, manganese superoxide dismutase plays an important role in detoxification of superoxide before it interferes with mitochondrial function and causes programmed cell death. here, we investigated the role of leishmania donovani mitochondrial iron superoxide dismutase-a (ldfesoda) in protecting the parasite from oxidative stress and in the control of pro ... | 2012 | 22342963 |
| cloning, overexpression and characterization of leishmania donovani triosephosphate isomerase. | triosephosphate isomerase (tim) is a major enzyme in the glycolytic pathway, which catalyzes the interconversion of glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. here, we report cloning, expression and purification of a catalytically active recombinant tim of leishmania donovani (ldtim). the recombinant ldtim had a ph optimum in the range of 7.2-9.0, found stable at 25°c for 30 min and k(m) and v(max) for the substrate glyceraldehyde 3-phosphate was 0.328±0.02mm and 10.05mm/min/mg, r ... | 2012 | 22342510 |
| coibanoles, a new class of meroterpenoids produced by pycnoporus sanguineus. | three new terpenoids of mixed biosynthetic origin were isolated from the culture filtrate of the endophytic fungus pycnoporus sanguineus. their structures were determined by extensive spectroscopic analyses. we have named these tricyclic and tetracyclic metabolites 'coibanoles a-c' in reference to coiba island and coiba national park, panamá, from which the plant and endophyte were collected. the extract was inactive to the human parasites trypanosoma cruzi, leishmania donovani, and plasmodium f ... | 2012 | 25177062 |
| comparative modeling of hgprt enzyme of l. donovani and binding affinities of different analogs of gmp. | hypoxanthine-guanine phosphoribosyl transferase (hgprt; ec 2.4.2.8) is a central enzyme in the purine recycling pathway. parasitic protozoa (leishmania donovani) cannot synthesize purines de novo and utilize the salvage pathway to produce purine bases. thus, this enzyme is targeted in drug discovery and development. the model of the monomeric l. donovani hgprt showed that this enzyme is an α/β type protein with a prtase type i folding pattern. among all of the computationally screened compounds, ... | 2012 | 22327112 |
| identification of novel s-adenosyl-l-homocysteine hydrolase inhibitors through homology-model-based virtual screening, synthesis, and biological evaluation. | the present study describes a successful application of computational approaches to identify novel leishmania donovani (ld) adohcyase inhibitors utilizing the differences for ld adohcyase nad(+) binding between human and ld parasite. the development and validation of the three-dimensional (3d) structures of ld adohcyase using the l. major adohcyase as template has been carried out. at the same time, cloning of the ld adohcyase gene from clinical strains, its overexpression and purification have ... | 2012 | 22324915 |
| comparative study of rk39 leishmania antigen for serodiagnosis of visceral leishmaniasis: systematic review with meta-analysis. | the rk39 recombinant protein is derived from a specific antigen produced by the leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. we present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rk39 antigen in comparison to the use of other antigen preparations. | 2012 | 22303488 |
| biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of leishmania donovani. | resistance to antimony is a major cause of failure to therapy in a large proportion of visceral leishmaniasis cases. methods to distinguish resistant and sensitive parasite are urgently needed as the standard in vitro intracellular drug susceptibility assays are cumbersome and time consuming. differential expression profiling studies have led to the identification of several antimony resistance-associated genes; however, their efficacy as a potential biomarker for monitoring antimony resistance ... | 2012 | 22302478 |
| therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis. | therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. here, we describe the development of an adenovirus-based vaccine (ad5-kh) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2a sequence. in nonvaccinated leishmania donovani-infected balb/c mice, haspb- and kmp11-specific cd8(+) t cell responses were undetectable, although igg1 and igg2a antibodies ... | 2012 | 22301630 |
| the anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. | safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of asia, africa, and latin america. here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating african trypanosomiasis, shows promise for treating visceral leishmaniasis. this 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. both me ... | 2012 | 22301556 |