Publications

aminothiazoles: hit to lead development to identify antileishmanial agents.	as part of drugs for neglected diseases initiative's lead optimization program for the development of new chemical entities to treat visceral leishmaniasis (vl), a series of aminothiazoles were synthesized and screened for in vitro efficacy, solubility and microsomal stability. the primary aim of identifying a lead structure with sub-micromolar activity was achieved. out of 43 compounds synthesized, 16 compounds showed in vitro activity at less than 1 μm against vl. compound 32 showed excellent ...	2015	26318065
cross reactive molecules of human lymphatic filaria brugia malayi inhibit leishmania donovani infection in hamsters.	coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. earlier we showed that immunization with bmafii (sephadex g-200 eluted) fraction of human lymphatic filaria brugia malayi inhibited progression of leishmania donovani infection in golden hamsters. in the present study we identified cross reactive molecules of b. malayi, and investigated their effect on l. donovani infection and associated imm ...	2015	26341753
discovery of potent nitrotriazole-based antitrypanosomal agents: in vitro and in vivo evaluation.	3-nitro-1h-1,2,4-triazole- and 2-nitro-1h-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. all 3-nitrotriazole-based derivatives were extremely potent anti-trypanosoma cruzi agents at sub nm concentrations and exhibited a high degree of selectivity for the parasite. the 2-nitroimidazole analogs were only moderately active against t. cruzi amastigotes and exhibited low selectivity. both types of compound were active against leishmania d ...	2015	26344593
characterisation of cutaneous leishmaniasis in matara district, southern sri lanka: evidence for case clustering.	leishmaniasis is a neglected tropical disease transmitted by phlebotomus spp. sand flies. cutaneous leishmaniasis (cl) in sri lanka is caused by leishmania donovani. transmission patterns are different in southern and northern sri lanka. current study examined the prevalence, risk factors and distribution of cl in matara district, southern sri lanka. total of 2260 individuals from four district secretariat divisions (dsds) were screened by house to house surveys using an interviewer administered ...	2015	26345305
glycyrrhizic acid-mediated subdual of myeloid-derived suppressor cells induces antileishmanial immune responses in a susceptible host.	cd11b(+) gr1(+) myeloid-derived suppressor cells (mdscs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing t cell functions. we observed that cd11b(+) gr1(+) mdscs, which initially expanded in soluble leishmanial antigen (sla)-immunized mice and later diminished, suppressed proliferation of t cells isolated from sla-immunized mice, but to a lesser extent than the case in naive mice. this lesser suppression of mdscs accompan ...	2015	26351281
novel inhibitors of ornithine decarboxylase of leishmania parasite (ldodc): the parasite resists ldodc inhibition by overexpression of spermidine synthase.	ornithine decarboxylase (ldodc), a key enzyme in polyamine biosynthesis in leishmania donovani, catalyzes the conversion of ornithine to putrescine that is finally used for synthesis of spermidine and other polyamines. inhibition of ornithine decarboxylase is likely to deplete the parasite trypanothione and may result in increased reactive oxygen species (ros). sequence as well as structure of ldodc and human odc shows significant difference; therefore, we have identified novel specific inhibito ...	2016	26362015
3-nitrotriazole-based piperazides as potent antitrypanosomal agents.	novel linear 3-nitro-1h-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. in addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. most 3-nitrotriazole-based derivatives were potent and selective against trypanosoma cruzi parasites, but only one displayed these desired properties against trypanosoma brucei rhodesiense. moreover, two 3-nitrotriazole-based chlorophenylpiperazides were mod ...	2015	26363868
differential immune response against recombinant leishmania donovani peroxidoxin 1 and peroxidoxin 2 proteins in balb/c mice.	we assessed the immune response against recombinant proteins of two related, albeit functionally different, peroxidoxins from leishmania donovani: peroxidoxin 1 (ldpxn1) and peroxidoxin 2 (ldpxn2) in balb/c mice. we also evaluated the effect of coadministration of tlr agonists (cpg odn and gla-se) on the antigen-specific immune response. immunization with recombinant ldpxn1 alone induced a predominantly th2 type immune response that is associated with the production of high level of igg1 and no ...	2015	26380320
first evidence of leishmania infection in european brown hare (lepus europaeus) in greece: gis analysis and phylogenetic position within the leishmania spp.	although the existence of a sylvatic transmission cycle of leishmania spp., independent from the domestic cycle, has been proposed, data are scarce on leishmania infection in wild mammals in greece. in this study, we aimed to investigate the presence of leishmania infection in the european brown hare in greece, to infer the phylogenetic position of the leishmania parasites detected in hares in greece, and to identify any possible correlation between leishmania infection in hares with environment ...	2016	26386969
novel agents against miltefosine-unresponsive leishmania donovani.	visceral leishmaniasis is a deadly endemic disease. unresponsiveness to the only available oral drug miltefosine poses a big challenge for the chemotherapy of the disease. we report a novel molecule, ps-203 {4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester}, as effective against a miltefosine-unresponsive strain of the parasite. further, combinations of ps-203 with miltefosine were also evaluated and showed promising results against a miltefosine-unresponsive strai ...	2015	26392497
the tcp1γ subunit of leishmania donovani forms a biologically active homo-oligomeric complex.	chaperonins are a class of molecular chaperons that encapsulate nascent or stress-denatured proteins and assist their intracellular assembly and folding in an atp-dependent manner. the ubiquitous eukaryotic chaperonin, tcp1 ring complex is a hetero-oligomeric complex comprising two rings, each formed of eight subunits that may have distinct substrate recognition and atp hydrolysis properties. in leishmania, only the tcp1γ subunit has been cloned and characterized. it exhibited differential expre ...	2015	26395202
development and comparative evaluation of two antigen detection tests for visceral leishmaniasis.	visceral leishmaniasis (vl) can be fatal without timely diagnosis and treatment. treatment efficacies vary due to drug resistance, drug toxicity and co-morbidities. it is important to monitor treatment responsiveness to confirm cure and curtail relapse. currently, microscopy of spleen, bone marrow or lymph node biopsies is the only definitive method to evaluate cure. a less invasive test for treatment success is a high priority for vl management.	2015	26395447
targeting lysine deacetylases (kdacs) in parasites.	due to an increasing problem of drug resistance among almost all parasites species ranging from protists to worms, there is an urgent need to explore new drug targets and their inhibitors to provide new and effective parasitic therapeutics. in this regard, there is growing interest in exploring known drug leads of human epigenetic enzymes as potential starting points to develop novel treatments for parasitic diseases. this approach of repurposing (starting with validated targets and inhibitors) ...	2015	26402733
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
exploring the inhibitory activity of withaferin-a against pteridine reductase-1 of l. donovani.	withaferin a is an abundant withanolide present in withania somnifera leaves and to some extent in roots. it has been known for its profound anti-cancer properties, but its role in counteracting the leishmania donovani infection has to be explored. pteridine reductase 1 (ptr1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. we employed molecular docking studies to identify the bind ...	2016	26406482
development and validation of a novel leishmania donovani screening cascade for high-throughput screening using a novel axenic assay with high predictivity of leishmanicidal intracellular activity.	visceral leishmaniasis is an important parasitic disease of the developing world with a limited arsenal of drugs available for treatment. the existing drugs have significant deficiencies so there is an urgent need for new and improved drugs. in the human host, leishmania are obligate intracellular parasites which poses particular challenges in terms of drug discovery. to achieve sufficient throughput and robustness, free-living parasites are often used in primary screening assays as a surrogate ...	2015	26407168
counteractive functions are encrypted in the residues of cd154.	cd40, as a single receptor that binds cd154 (cd40-ligand or cd40l), regulates counteractive effector functions such as production of pro- and anti-inflammatory cytokines. therefore, we examined whether such dual messages are encrypted in cd40l. as such message encryption was never investigated, we hypothesized that mutation of certain amino acid residues should in principle enhance pro-inflammatory cytokine production whereas mutation of some others would enhance anti-inflammatory cytokine secre ...	2015	26429321
phytochemical composition, antiparasitic and α-glucosidase inhibition activities from pelliciera rhizophorae.	panama has an extensive mangrove area and it is one of the countries with the highest biodiversity in america. mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in america. given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. this study was designed to evaluate the potential of pelliciera ...	2015	26435737
synthesis of unsymmetrical sulfides and their oxidation to sulfones to discover potent antileishmanial agents.	unsymmetrical sulfides were first synthesized using combinations of a 1,3-dicarbonyl, an aromatic aldehyde and a thiol in the presence of 10 mol % ethanolic piperidine. these sulfides derivatives were subsequently converted into corresponding sulfones via oxidation in the presence of m-chloroperoxybenzoic acid (m-cpba) at ice-bath to room temperature. the former reaction was achieved at room temperature through one-pot three-component. the later was obtained in good yields using mild reaction co ...	2015	26441303
protein kinase a signaling during bidirectional axenic differentiation in leishmania.	parasitic protozoa of the genus leishmania are obligatory intracellular parasites that cycle between the phagolysosome of mammalian macrophages, where they proliferate as intracellular amastigotes, and the midgut of female sand flies, where they proliferate as extracellular promastigotes. shifting between the two environments induces signaling pathway-mediated developmental processes that enable adaptation to both host and vector. developmentally regulated expression and phosphorylation of prote ...	2016	26460237
bioactive phloroglucinols from mallotus oppositifolius.	the two new acylphloroglucinol derivatives, methylene-bis-aspidinol ab (1) and mallopposinol (2), together with the nine known compounds, aspidinol b (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of mallotus oppositifolius. their structures were elucidated by spectral analysis including ms, 1d and 2d-nmr spectroscopy. in vitro trypanocidal and antileishmanial acti ...	2015	26463755
comparative fitness of a parent leishmania donovani clinical isolate and its experimentally derived paromomycin-resistant strain.	paromomycin has recently been introduced for the treatment of visceral leishmaniasis and emergence of drug resistance can only be appropriately judged upon its long term routine use in the field. understanding alterations in parasite behavior linked to paromomycin-resistance may be essential to assess the propensity for emergence and spread of resistant strains. a standardized and integrated laboratory approach was adopted to define and assess parasite fitness of both promastigotes and amastigot ...	2015	26469696
poly(amidoamine) dendrimers show carbonic anhydrase inhibitory activity against α-, β-, γ- and η-class enzymes.	four generations of poly(amidoamine) (pamam) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (cas, ec 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. the following bacterial, fungal and protozoan organisms were included in the study: vibrio cholerae, trypanosoma cruzi, leishmania donovani chagasi, porphyromonas gingivalis, cryptococcus neoformans, candida glabrata, and plas ...	2015	26476668
leishmania donovani-specific ub-related modifier-1: an early endosome-associated ubiquitin-like conjugation in leishmania donovani.	protein modification by ubiquitin (ub) and ub-like molecules (ubls) is a diverse biological process that regulates the activity of the target proteins. systematic studies of ubls in trypanosomatids like leishmania, the causative organism of potentially fatal visceral leishmaniasis, would yield a better understanding of the disease pathogenesis and identify novel therapeutic targets. the present study is the first to characterize leishmania donovani-specific ub-related modifier-1 (ldurm1) and the ...	2016	26481108
correction: combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection.		2015	26485528
implications of co-infection of leptomonas in visceral leishmaniasis in india.	protozoan parasites leishmania donovani (family: trypanosomatidae) cause fatal visceral leishmaniasis (vl) and the infection relapses in apparently cured population as post kala-azar dermal leishmaniasis (pkdl) in the indian subcontinent. in recent years co-infection of another trypanosomatid parasite leptomonas with l. donovani during vl/pkdl in this region has become prominent. the observation of clinically lesser-known insect parasite, leptomonas in leishmaniasis is intriguing to researchers. ...	2015	26492813
clinico-epidemiological analysis of post kala-azar dermal leishmaniasis (pkdl) cases in india over last two decades: a hospital based retrospective study.	patients with post kala-azar dermal leishmaniasis (pkdl) are considered a reservoir of leishmania donovani. it is imperative to identify and treat them early for control of visceral leishmaniasis (vl), a current priority in the indian subcontinent. we explored trends in clinico-epidemiological features of pkdl cases over last two decades, for improving management of the disease.	2015	26503551
specific k39 antibody response and its persistence after treatment in patients with imported leishmaniasis.	the sensitivity of a k39 elisa (leishmania igg, virion/serion) for the detection of antibodies in patients with imported leishmaniasis was compared with an immunofluorescence assay (ifa), which was applied as "golden standard". the retrospective study comprised 93 ifa-positive or borderline sera from 42 patients with visceral (n = 16) or cutaneous (n = 26) leishmaniasis. patients had acquired infection predominately in the mediterranean area or the middle east. the leishmania species (leishmania ...	2016	26508007
synthesis and biological evaluation of polyalthic acid derivatives for the treatment of neglected diseases.	polyalthic acid is a naturally occurring diterpene found in copaiba oil, one of the most popular natural medicines in the amazon. based on the reported antileishmanial activity of copaiba oil, a series of amides and diols derivatives of polyalthic acid were synthesized and tested against leishmania donovani and trypanosoma brucei. polyalthic acid was active in both assays with ic50 ranging from 3.87 to 8.68 μg/ml. the compound with best antileishmanial activity was 2 h (ic50=3.84 μg/ml) and comp ...	2015	26520665
short-course treatment regimen of indian visceral leishmaniasis with an indian liposomal amphotericin b preparation (fungisome™).	india bears the burden of about half of global visceral leishmaniasis (vl) cases with emerging problems of stibanate resistance. liposomal preparations have improved treatment outcome through shorter duration of therapy and lower toxicity compared with conventional amphotericin b. we report the efficacy of two short-course regimens of an indian preparation of liposomal amphotericin b (fungisome™) for vl caused by leishmania donovani in india. an open-label, randomized, single-center comparative ...	2016	26526926
downregulation of host tryptophan-aspartate containing coat (taco) gene restricts the entry and survival of leishmania donovani in human macrophage model.	leishmania are obligate intracellular protozoan parasites of mammalian hosts. promastigotes of leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. phagosomal maturation arrest is known to play a crucial role in the survival of pathogenic leishmania within activated macrophages. recently, tryptophan-aspartate containing coat (taco) gene has been recognized as playing a central role in the survival of mycobacterium tuberculosi ...	2015	26528242
il-17a-producing γδ t cells suppress early control of parasite growth by monocytes in the liver.	intracellular infections, such as those caused by the protozoan parasite leishmania donovani, a causative agent of visceral leishmaniasis (vl), require a potent host proinflammatory response for control. il-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. however, there are conflicting reports on the exact roles for il-17 during parasitic infections and limited knowledge about cellular sources and the immune p ...	2015	26538396
synthesis and antileishmanial evaluation of some 2,3-disubstituted-4(3h)-quinazolinone derivatives.	leishmaniasis is a neglected tropical parasitic diseases affecting millions of people around the globe. quinazolines are a group of compounds with diverse pharmacological activities. owing to their promising antileishmanial activities, some 3-aryl-2-(substitutedstyryl)-4(3h)-quinazolinones were synthesized in good yields (65.2% to 86.4%).	2014	26548988
molecular docking and structure-based virtual screening studies of potential drug target, caax prenyl proteases, of leishmania donovani.	targeting caax prenyl proteases of leishmania donovani can be a good approach towards developing a drug molecule against leishmaniasis. we have modeled the structure of caax prenyl protease i and ii of l. donovani, using homology modeling approach. the structures were further validated using ramachandran plot and prosa. active site prediction has shown difference in the amino acid residues present at the active site of caax prenyl protease i and caax prenyl protease ii. the electrostatic potenti ...	2016	26551589
cinnamic acid bornyl ester derivatives from valeriana wallichii exhibit antileishmanial in vivo activity in leishmania major-infected balb/c mice.	human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by leishmania major or leishmania donovani, respectively. some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileish ...	2015	26554591
toll-like receptor 2 targeted rectification of impaired cd8⁺ t cell functions in experimental leishmania donovani infection reinstates host protection.	leishmania donovani, a protozoan parasite, causes the disease visceral leishmanisis (vl), characterized by inappropriate cd8+ t-cell activation. therefore, we examined whether the toll-like receptor 2 (tlr2) ligand ara-lam, a cell wall glycolipid from non-pathogenic mycobacterium smegmatis, would restore cd8+ t-cell function during vl. we observed that by efficient upregulation of tlr2 signaling-mediated nf-κb translocation and mapk signaling in cd8+ t-cells (cd25+cd28+il-12r+ifn-γr+), ara-lam t ...	2015	26559815
comparative study of structural models of leishmania donovani and human gdp-mannose pyrophosphorylases.	leishmania is the parasite responsible for the neglected disease leishmaniasis. its virulence and survival require biosynthesis of glycoconjugates, whose guanosine diphospho-d-mannose pyrophosphorylase (gdp-mp) is a key player. however, experimentally resolved structures of this enzyme are still lacking. we herein propose structural models of the gdp-mp from human and leishmania donovani. based on a multiple sequences alignment, the models were built with modeller and then carefully refined with ...	2016	26562546
il-17a promotes susceptibility during experimental visceral leishmaniasis caused by leishmania donovani.	leishmania donovani is an intracellular parasite that infects professional phagocytes and causes visceral leishmaniasis (vl). the immune response during vl has been extensively studied in the context of t-helper (th)1 and th2 responses. immunity against this parasite is dependent on ifn-γ production and subsequent macrophage activation, and the th2 response promotes granuloma formation. the cytokine il-17a is associated with neutrophilic inflammation. depletion of neutrophils during experimental ...	2016	26581600
leishmania donovani encodes a functional selenocysteinyl-trna synthase.	the synthesis of selenocysteine, the 21st amino acid, occurs on its transfer rna (trna), trna(sec). trna(sec) is initially aminoacylated with serine by seryl-trna synthetase and the resulting seryl moiety is converted to phosphoserine by o-phosphoseryl-trna kinase (pstk) in eukaryotes. the selenium donor, selenophosphate is synthesized from selenide and atp by selenophosphate synthetase. selenocysteinyl-trna synthase (sepsecs) then uses the o-phosphoseryl-trna(sec) and selenophosphate to form se ...	2016	26586914
anti-infective assessment of senecio smithioides (asteraceae) and isolation of 9-oxoeuryopsin, a furanoeremophilane-type sesquiterpene with antiplasmodial activity.	the search for anti-infective activity in the antipyretic plant senecio smithioides was conducted. petroleum ether (pe), dichloromethane (ch2cl2), ethyl acetate (etoac) and hydroethanolic (96% etoh) extracts, and compounds 9-oxoeuryopsin (1), epoxydecompostin (2) and senecionine (3) were obtained from the aerial parts. all extracts and 1 were tested against chloroquine-resistant strain of plasmodium falciparum (ref. chloroquine), trypanosoma cruzi (ref. nifurtimox), leishmania braziliensis, leis ...	2015	26606687
impaired snx9 expression in immune cells during chronic inflammation: prognostic and diagnostic implications.	chronic inflammation is associated with immunosuppression and downregulated expression of the tcr cd247. in searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (snx9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. snx9 expression was affected earlier than cd247 by the generated harmful environment, suggesting that i ...	2016	26608909
establishment of correlation between in-silico and in-vitro test analysis against leishmania hgprt to inhibitors.	hypoxanthine phosphoribosyltransferase (hgprt; ec 2.4.2.8) is a central enzyme in the purine recycling pathway of all protozoan parasites. protozoan parasites cannot synthesize purine bases (dna/rna) which is essential for survival as lack of de-novo pathway. thus its good target for drug design and discovery as inhibition leads to cessation of replication. prtase (transferase enzyme) has common prtase type i folding pattern domain for its activities. genomic studies revealed the sequence patter ...	2016	26616453
a new bisbenzylisoquinoline alkaloid isolated from thalictrum foliolosum, as a potent inhibitor of dna topoisomerase ib of leishmania donovani.	chemical investigation of the stem of thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). the structures of the new compounds were established by detailed 2d nmr spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. inhibitory activities of these four compounds against dna t ...	2016	26625837
pathogenicity of leishmania donovani is associated with the high expression of a group low molecular weight proteins.	with few exceptions, members of the leishmania donovani complex such as l. donovani, l. infantum and l. chagashi are the etiological agents of visceral leishmaniasis or kala-azar. promastigotes of leishmania spp. lose their pathogenicity; the ability to establish infection in a susceptible host, after prolonged culture. the molecular basis of this evolution of pathogenic to nonpathogenic culture has not been very well understood. it has been proposed that the loss of pathogenicity is associated ...	2017	26629453
induction of apoptosis by zerumbone isolated from zingiber zerumbet (l.) smith in protozoan parasite leishmania donovani due to oxidative stress.	in the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against leishmania infection. various ginger spices of the zingiberaceae family are widely used as spices, flavouring agents, and medicines in southeast asia because of their unique flavour as well as due to their medicinal properties. zerumbone, a natural component of zingiber zerumbet (l.) s ...	2016	26643969
development of plga-peg encapsulated miltefosine based drug delivery system against visceral leishmaniasis.	targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated plga–peg nanoparticles (ppem) to target macrophage of infected tissues against leishmania donovani. the structural characterization of plga–peg by transmission electron microscopy (tem) has shown a size range of 10 to 15 nm. synthesis and drug encapsulation confirmed by dynamic light scattering (dls) and fourier transform infrared spectrosc ...	2016	26652429
in vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl β-cyclodextrin formulation and pharmacokinetics via intravenous route.	2-n-propylquinoline (2-n-pq) had shown interesting in vivo antileishmanial activities after administration by oral route on leishmaniasis animal models. however, the lipophilic properties of this compound avoid its use by intravenous route, this route being indicated in cases of severe visceral leishmaniasis with vomiting. thus, a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin (2-n-pq-hpc) formulation was set up in this aim. the formulation was active in vitro both on leishmania donovani ax ...	2015	26653559
identification and characterization of a leishmania donovani serine protease inhibitor: possible role in regulation of host serine proteases.	this study aims to identify, purify, and characterize an endogenous serine protease inhibitor from an indian strain of leishmania donovani, which causes the fatal visceral leishmaniasis.	2016	26656469
antiproteolytic and leishmanicidal activity of coccinia grandis (l.) voigt leaf extract against leishmania donovani promastigotes.	in visceral leishmaniasis (vl), development of alternative safe therapeutic strategy is gaining paramount wherein natural components of plant origin have prominence. we explored coccinia grandis (l.) voigt, a medicinal plant known in traditional folk medicine, for its antileishmanial efficacy. sds-page analysis of the c. grandis leaf extract (cg-ex) showed few protein bands about 14-66 kda among which three (64.8, 55.8 and 15.3 kda) were identified as serine protease inhibitors by reverse zymogr ...	2015	26669017
bioactivity guided fractionation of moringa oleifera lam. flower targeting leishmania donovani.	leishmaniases is a group of diseases caused by the protozoan parasite belonging to the genus leishmania. at least 20 species of leishmania are known to infect humans transmitted by female sandflies, phlebotomus spp. leishmania donovani causes visceral leishmaniasis, considered most lethal among the common three forms of leishmaniasis. lack of appropriate vaccines, emergence of drug resistance and side effects of currently used drugs stress the need for better alternative drugs, particularly from ...	2015	26669018
leishmania donovani exploits myeloid cell leukemia 1 (mcl-1) protein to prevent mitochondria-dependent host cell apoptosis.	apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. in the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (mcl-1) is exploited by the intra-macrophage parasite leishmania donovani to protect their "home" from actinomycin d-induced mitochondria-dependent apoptosis. ...	2016	26670606
polymerase chain reaction detection of leishmania dna in skin biopsy samples in sri lanka where the causative agent of cutaneous leishmaniasis is leishmania donovani.	leishmania donovani is the known causative agent of both cutaneous (cl) and visceral leishmaniasis in sri lanka. cl is considered to be under-reported partly due to relatively poor sensitivity and specificity of microscopic diagnosis. we compared robustness of three previously described polymerase chain reaction (pcr) based methods to detect leishmania dna in 38 punch biopsy samples from patients presented with suspected lesions in 2010. both, leishmania genus-specific jw11/jw12 kdna and litsr/l ...	2015	26676321
leptin induces the phagocytosis and protective immune response in leishmania donovani infected thp-1 cell line and human pbmcs.	visceral leishmaniasis (vl) is an infectious disease responsible for several deaths in malnourished children due to impaired cell-mediated immunity, which is accompanied by low circulating leptin levels. the cytokine function of leptin is implicated for several immune regulation activities such as hematopoiesis, angiogenesis, innate and adaptive immunity. its deficiency associated with polarization of th2 response, which coincides with vl pathogenesis. to determine the cytokine role of leptin in ...	2016	26688099
leishmanicidal activity of piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by th1 immunostimulatory potential in vivo.	visceral leishmaniasis (vl) is a life-threatening protozoal infection chiefly impinging the rural and poor population in the tropical and sub-tropical countries. the deadly aﬄiction is rapidly expanding after its association with aids, swiftly defying its status of a neglected disease. despite successful formulation of vaccine against canine leishmaniasis, no licensed vaccine is yet available for human vl, chemotherapy is in appalling state, and the development of new candidate drugs has been pa ...	2015	26696979
in vitro selection of miltefosine resistance in promastigotes of leishmania donovani from nepal: genomic and metabolomic characterization.	in this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (mil) resistance in two clinically derived leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain sb-s; and antimony resistant sb-r). mil-r was easily induced in both strains using the promastigote-stage, but a significant increase in mil-r in the intracellular amastigote compared to the corresponding wild-type did not occur ...	2016	26713880
immunomodulation mediated through leishmania donovani protein disulfide isomerase by eliciting cd8+ t-cell in cured visceral leishmaniasis subjects and identification of its possible hla class-1 restricted t-cell epitopes.	protein disulphide isomerase (pdi) is one of the key enzymes essential for the survival of leishmania donovani in the host. our study suggested that pdi is associated with the generation of th1-type of cellular responses in treated visceral leishmaniasis (vl) subjects. the stimulation of peripheral blood mononuclear cells (pbmcs) with recombinant protein disulphide isomerase upregulated the reactive oxygen species generation, nitric oxide release, il12 and ifn-γ production indicating its pivotal ...	2017	26727289
evaluation of in vitro antiprotozoal activity of ajuga laxmannii and its secondary metabolites.	context some ajuga l. (lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. objective in the continuation of our studies on the identification of antiprotozoal secondary metabolites of turkish lamiaceae species, we have investigated the aerial parts of ajuga laxmannii. materials and methods the aerial parts of a. laxmannii were extracted with meoh. the h2o subextract was subjected to polyamide, c18-mplc an ...	2016	26734766
up-regulation of cytosolic tryparedoxin in amp b resistant isolates of leishmania donovani and its interaction with cytosolic tryparedoxin peroxidase.	leishmania is a unicellular protozoan parasite which causes leishmaniasis, a neglected tropical disease. it possess a unique thiol metabolism comprising of several proteins among which, tryparedoxin (ctxn) and tryparedoxin peroxidase (ctxnpx), function in concert as oxidoreductases, utilizing trypanothione as a source of electrons to reduce the hydroperoxides produced by macrophages during infection. this detoxification pathway is unique and essential for the survival of leishmania. herein, we r ...	2016	26743980
up regulation of a2b adenosine receptor on monocytes are crucially required for immune pathogenicity in indian patients exposed to leishmania donovani.	adenosine, an endogenous purine nucleoside is one such extracellular signalling molecule whose role in regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is not fully understood. here, we investigated the relationship between leishmania donovani infection and expression of a2b receptor on monocytes in vl patients in their pre and post treatment stage. we also investigated the molecular mechanisms influencing the interaction between immunopathogenicity an ...	2016	26748211
intradermal immunization of leishmania donovani centrin knock-out parasites in combination with salivary protein ljm19 from sand fly vector induces a durable protective immune response in hamsters.	visceral leishmaniasis (vl) is a neglected tropical disease and is fatal if untreated. there is no vaccine available against leishmaniasis. the majority of patients with cutaneous leishmaniasis (cl) or vl develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. we have previously report ...	2016	26752686
simple and efficient synthesis of 5'-aryl-5'-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities.	a series of non-hydrolysable 5'-aryl substituted gdp analogs has been synthesized by reacting 5'-azido-5'-deoxyguanosine with different aryl- and benzyloxy-alkynes. cu(i) nanoparticles in water were found to be the most efficient catalyst, producing the desired 5'-arylguanosines with good yields. the synthesized compounds were screened for in vitro antileishmanial activity against leishmania donovani axenic amastigotes and intramacrophage amastigotes stages. the 4-(3-nitrobenzyl)-1,2,3-triazole ...	2016	26754628
host-mediated leishmania donovani treatment using ar-12 encapsulated in acetalated dextran microparticles.	leishmaniasis is a disease caused by parasites of leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. the current treatments for visceral leishmaniasis (vl), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. one way to limit emergence of resistant pathogens is th ...	2016	26768723
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
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
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
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
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
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
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
understanding the transmission dynamics of leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in bihar, india.	visceral leishmaniasis (vl) is a neglected vector-borne disease. in india, it is transmitted to humans by leishmania donovani-infected phlebotomus argentipes sand flies. in 2005, vl was targeted for elimination by the governments of india, nepal and bangladesh by 2015. the elimination strategy consists of rapid case detection, treatment of vl cases and vector control using indoor residual spraying (irs). however, to achieve sustained elimination of vl, an appropriate post elimination surveillanc ...	2016	26812963
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
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
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
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
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
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
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
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
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
serological assessment for leishmania donovani infection in blood donors of sunsari district, dharan, nepal.	visceral leishmaniasis (vl) is a major vector-borne disease caused by leishmania donovani, after replication of the parasites in macrophages, mononuclear phagocytic system. vl is endemic in 12 districts of central and eastern terai lowlands of nepal bordering north bihar, india with an estimated 8 million population at risk. in addition, vl endemicity is also extending to new endemic regions like dharan from its classical rural foci. hence, we aimed to detect the evidence of leishmania donovani ...	2016	26855514
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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