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leishmania donovani utilize sialic acids for binding and phagocytosis in the macrophages through selective utilization of siglecs and impair the innate immune arm.leishmania donovani, belonging to a unicellular protozoan parasite, display the differential level of linkage-specific sialic acids on their surface. sialic acids binding immunoglobulin-like lectins (siglecs) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with the linkage-specific sialic acids. here we aimed to explore the utilization of sialic acids by leishmania donovani for siglec-mediated binding, phagocytosis, modulation of innate immune response ...201627494323
visceral leishmaniasis on the indian subcontinent: modelling the dynamic relationship between vector control schemes and vector life cycles.visceral leishmaniasis (vl) is a disease caused by two known vector-borne parasite species (leishmania donovani, l. infantum), transmitted to man by phlebotomine sand flies (species: phlebotomus and lutzomyia), resulting in ≈50,000 human fatalities annually, ≈67% occurring on the indian subcontinent. indoor residual spraying is the current method of sand fly control in india, but alternative means of vector control, such as the treatment of livestock with systemic insecticide-based drugs, are be ...201627537774
the potential use of forensic dna methods applied to sand fly blood meal analysis to identify the infection reservoirs of anthroponotic visceral leishmaniasis.in the indian sub-continent, visceral leishmaniasis (vl), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite leishmania donovani and transmitted by the sand fly phlebotomus argentipes. vl is prevalent in northeast india where it is believed to have an exclusive anthroponotic transmission cycle. there are four distinct cohorts of l. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured vl cas ...201627192489
measures to control phlebotomus argentipes and visceral leishmaniasis in india.visceral leishmaniasis is a deadly parasitic disease that is transmitted via the bite of a female sand fly, phlebotomus argentipes. the highest burden of this disease is in northern india. in 2005, india embarked on an initiative with nepal, bangladesh, and the world health organization to eliminate visceral leishmaniasis by 2015. with the goal of 1 case in 10,000 people still unmet, it is prudent to evaluate the tools that have been used thus far to reduce vector numbers and cases of the diseas ...201627308270
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 ...201626812963
seroepidemiology and molecular diversity of leishmania donovani complex in georgia.leishmaniasis includes multiple clinical syndromes, most notably visceral, cutaneous, and mucosal forms. visceral leishmaniasis (vl), also known as kala-azar, is a potentially fatal disease endemic to large parts of africa and asia, and in south-eastern europe (greece, turkey, georgia). visceral leishmaniasis is a parasitic zoonosis caused by species of the l. donovani complex. in the classical epidemiological model the main reservoir for vl are canines.201627177688
a review of visceral leishmaniasis during the conflict in south sudan and the consequences for east african countries.visceral leishmaniasis (vl), caused predominantly by leishmania donovani and transmitted by both phlebotomus orientalis and phlebotomus martini, is highly endemic in east africa where approximately 30 thousands vl cases are reported annually. the largest numbers of cases are found in sudan - where phlebotomus orientalis proliferate in acacia forests especially on sudan's eastern border with ethiopia, followed by south sudan, ethiopia, somalia, kenya and uganda. long-standing civil war and unrest ...201627549162
in vitro permissiveness of bovine neutrophils and monocyte derived macrophages to leishmania donovani of ethiopian isolate.epidemiological studies in ethiopia have documented that the risk of visceral leishmaniasis (vl, kala-azar) is higher among people living with domestic animals. the recent report on isolation of leishmania donovani complex dna and the detected high prevalence of anti-leishmanial antibodies in the blood of domestic animals further strengthen the potential role of domestic animals in the epidemiology of vl in ethiopia. in mammalian hosts polymorphonuclear cells (pmn) and macrophages are the key im ...201627090082
drug repurposing: mining protozoan proteomes for targets of known bioactive compounds.to identify potential opportunities for drug repurposing by developing an automated approach to pre-screen the predicted proteomes of any organism against databases of known drug targets using only freely available resources.201623757409
prevalence of zoonotic and vector-borne infections among afghan national army recruits in afghanistan.to measure prevalence of prior/current plasmodium vivax and plasmodium falciparum (pv and pf), brucella spp. (br), dengue virus (denv), leishmania donovani (visceral leishmaniasis; vl), and crimean-congo hemorrhagic fever (cchf) virus exposure among afghan national army (ana) recruits.201627304051
structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.calreticulin (crt) is a multifaceted protein, initially discovered as an endoplasmic reticulum (er) chaperone protein, that is essential in calcium metabolism. various implications in cancer, early development and immunology have been discovered more recently for crt, as well as its role as a dominant 'eat-me' prophagocytic signal. intriguingly, cell-surface exposure/secretion of crt is among the infective strategies used by parasites such as trypanosoma cruzi, entamoeba histolytica, taenia soli ...201627840680
structure-based design of inhibitors of the crucial cysteine biosynthetic pathway enzyme o-acetyl serine sulfhydrylase.the cysteine biosynthetic pathway is of fundamental importance for the growth, survival, and pathogenicity of the many pathogens. this pathway is present in many species but is absent in mammals. the ability of pathogens to counteract the oxidative defences of a host is critical for the survival of these pathogens during their long latent phases, especially in anaerobic pathogens such as entamoeba histolytica, leishmania donovani, trichomonas vaginalis, and salmonella typhimurium. all of these o ...201626303427
terrenolide s, a new antileishmanial butenolide from the endophytic fungus aspergillus terreus.terrenolide s, a new butenolide derivative (6), together with six known compounds: (22e,24r)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin a (4), terretonin (5) and butyrolactone vi (7) have been isolated from the endophytic fungus aspergillus terreus isolated from the roots of carthamus lanatus (asteraceae). their structures were established by extensive spectroscopic analyses (1d, 2d nmr and hresims), as well as optical rotati ...201626299734
biochemical characterization of dihydroorotase of leishmania donovani: understanding pyrimidine metabolism through its inhibition.de novo pyrimidine biosynthesis pathway is well developed and functional in protozoan parasite leishmania donovani. the dihydroorotase (lddhoase) is third enzyme of the pathway. the enzyme was cloned, expressed in e. coli bl21 (de3), purified to homogeneity and biochemically characterized. the estimated kcat for the forward reaction and reverse reactions were 2.1 ± 0.1 s(-1) and 1.1 ± 0.15 s(-1), respectively. homology modeling and docking studies were done to find out potential inhibitors for l ...201627650727
statin-induced chronic cholesterol depletion inhibits leishmania donovani infection: relevance of optimum host membrane cholesterol.leishmania are obligate intracellular protozoan parasites that invade and survive within host macrophages leading to leishmaniasis, a major cause of mortality and morbidity worldwide, particularly among economically weaker sections in tropical and subtropical regions. visceral leishmaniasis is a potent disease caused by leishmania donovani. the detailed mechanism of internalization of leishmania is poorly understood. a basic step in the entry of leishmania involves interaction of the parasite wi ...201627319380
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 ...201626586914
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 ...201626855514
an unusual presentation of leishmaniasis in a human immunodeficiency virus-positive individual.leishmaniasis is a neglected tropical disease caused by vector-borne protozoa of the genus leishmania. cutaneous and mucocutaneous forms result in disfiguration or mutilation, whilst visceral leishmaniasis (vl) affects multiple organs and is fatal if untreated. notably, leishmania are capable of establishing a chronic infection, which may reactivate years after initial infection when the host becomes immune-suppressed.201628348746
synthesis and antileishmanial activity of c7- and c12-functionalized dehydroabietylamine derivatives.abietane-type diterpenoids, either naturally occurring or synthetic, have shown a wide range of pharmacological actions, including antiprotozoal properties. in this study, we report on the antileishmanial evaluation of a series of (+)-dehydroabietylamine derivatives functionalized at c7 and/or c12. thus, the activity in vitro against leishmania infantum, leishmania donovani, leishmania amazonensis and leishmania guyanensis, was studied. most of the benzamide derivatives showed activities at low ...201627318121
verbascoside inhibits promastigote growth and arginase activity of leishmania amazonensis.verbascoside (1) is a phenylethanoid glycoside that has antileishmanial activity against leishmania infantum and leishmania donovani. in this study, we verified the activity of 1 on leishmania amazonensis and arginase inhibition. compound 1 showed an ec50 of 19 μm against l. amazonensis promastigotes and is a competitive arginase inhibitor (ki = 0.7 μm). docking studies were performed to assess the interaction of 1 with arginase at the molecular level. arginase is an enzyme of the polyamine bios ...201627096224
synthesis and pharmacological evaluation of mono-arylimidamides as antileishmanial agents.arylimidamide (aia) compounds containing two pyridylimidamide terminal groups (bis-aias) possess outstanding in vitro antileishmanial activity, and the frontrunner bis-aia db766 (2,5-bis[2-(2-isopropoxy)-4-(2-pyridylimino)aminophenyl]furan) is active in visceral leishmaniasis models when given orally. eighteen compounds containing a single pyridylimidamide terminal group (mono-aias) were synthesized and evaluated for their antileishmanial potential. six of these compounds exhibited sub-micromola ...201627048943
effective anti-leishmanial activity of minimalist squaramide-based compounds.in order to evaluate the in vitro leishmanicidal activity of n,n'-squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against leishmania infantum, leishmania braziliensis and leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. infectivity and cytotoxicity tests were performed on j774.2 macrophage cells using meglumine anti ...201627480054
leishmania spp. in didelphis spp. from northeastern brazil.the synanthropic behavior of marsupials of the genus didelphis in endemic areas of leishmaniasis suggests that these animals may play an important role in the epidemiology of this infection. the aim of the present study was to detect leishmania spp. dna in didelphis albiventris (white-eared opossum) and didelphis aurita (big-eared opossum) living in forested and peridomestic areas of northeastern brazil. blood samples were collected from 25 animals (23 d. albiventris and 2 d. aurita ) by cardiac ...201627691942
mycobacterium indicus pranii (mw)-mediated protection against visceral leishmaniasis by reciprocal regulation of host dual-specificity phosphatases.leishmania donovani resides within the host macrophages by dampening host defence mechanisms and thereby it modulates the host cell functions for its survival. multiple host cell factors compete during the interplay between the host and the parasite. roles for dual-specificity phosphatases (dusps) are implicated in various pathological conditions. however, the reciprocity of these dusps was unknown in l. donovani infection in a susceptible model. here, we show that mycobacterium indicus pranii ( ...201628013190
leishmania recombinant antigen modulates macrophage effector function facilitating early clearance of intracellular parasites.immunmodulation combined with chemotherapy has emerged as an alternative to treat infections. the study evaluates immunomodulatory properties of a leishmania recombinant protein (ra6) in activating macrophages and clearing intracellular parasites.201627941165
a mitochondrial hsp70 (hspa9b) is linked to miltefosine resistance and stress response in leishmania donovani.protozoan parasites of the genus leishmania are responsible for leishmaniasis, a neglected tropical disease affecting millions worldwide. visceral leishmaniasis (vl), caused by leishmania donovani, is the most severe form of leishmaniasis with high rates of mortality if left untreated. current treatments include pentavalent antimonials and amphotericin b. however, high toxicity and emergence of resistance hinder the success of these options. miltefosine (hepc) is the first oral treatment availab ...201627906059
identification of b-cell epitope of leishmania donovani and its application in diagnosis of visceral leishmaniasis.diagnosis of visceral leishmaniasis (vl) is often hindered by cross-reactions with antigens from other related parasite infections. this study aimed to develop an immunochromatographic test (ict) which can detect the antigen present in circulating immune complexes (cics) of vl patients using b-cell epitope-specific antibodies. ms analysis of six immunoreactive 2de spots revealed two epitopes i.e. rffvqgdgigqhslqealerr (p1) and rrvavlvlldrl (p2) (from a hypothetical protein [acc no: xp_003861458. ...201627892844
in silico sequence analysis, homology modeling and function annotation of leishmanolysin from leishmania donovani.leishmaniases are a complex of diseases that range from the deadly visceral disease and some self-curing lesions to gross disfigurations. about 12 million peoples from 88 different countries get infected by this protozoan parasite through the sand flies. visceral leishmaniasis is a potentially fatal disease endemic to large parts of asia and africa, primarily caused by the protozoan parasite leishmania donovani. l. donovani is a species of leishmania, a hemoflagellate parasite and causative agen ...201627876928
phylogenetic position of leishmania isolates from khyber pakhtunkhwa province of pakistan.several species of the genus leishmania are causative agents of cutaneous leishmaniasis in pakistan. this study aimed to determine phylogenetic placement of leishmania species causing cutaneous leishmaniasis in khyber pakhtunkhwa province, pakistan (34 leishmania tropica, 3 leishmania infantum), in-relation to species from other geographical areas using gene sequences encoding cytochrome b (cytb) and internal transcribed spacer 2 (its2). based on cytochrome b sequence analysis, l. tropica strain ...201627233810
naloxonazine, an amastigote-specific compound, affects leishmania parasites through modulation of host-encoded functions.host-directed therapies (hdts) constitute promising alternatives to traditional therapy that directly targets the pathogen but is often hampered by pathogen resistance. hdt could represent a new treatment strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite leishmania. this protozoan develops exclusively within phagocytic cells, where infection relies on a complex molecular interplay potentially exploitable for drug targets. we previously identif ...201628036391
subcellular localization studies of ldbpk_070020, a conserved protein of leishmania donovani. 201628035116
the screening of novel inhibitors against leishmania donovani calcium ion channel to fight leishmaniasis.leishmania is an intracellular protozoan parasite which causes leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world. the current treatment which includes use of amphotericin b, antimonials, and others has major drawbacks due to toxicity, resistance, and extraordinary high cost. so there is an urgent need of development of new drug targets to fight against leishmaniasis. in this regard we have selected leishmania donovani ca2+ ion chan ...201628034363
nanotized curcumin and miltefosine, a potential combination for treatment of experimental visceral leishmaniasis.leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. combination therapies (ct) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. ct are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite leishmania in the present stu ...201728031196
novel β-carboline-quinazolinone hybrids disrupt leishmania donovani redox homeostasis and show promising antileishmanial activity.visceral leishmaniasis is a deadly parasitic disease caused by leishmania donovani. paucity exists in the discovery of novel chemotherapeutics against leishmaniasis. in this study, we synthesized a natural product inspired diversity oriented synthesis library of l. donovani trypanothione reductase (ldtr) inhibitor β-carboline-quinazolinone hybrids, which are different in stereochemical architecture and diverse in the bioactive chemical space. it is noteworthy that chirality affects drug-to-prote ...201728017772
leishmania donovani nucleoside hydrolase (nh36) domains induce t-cell cytokine responses in human visceral leishmaniasis.development of immunoprotection against visceral leishmaniasis (vl) focused on the identification of antigens capable of inducing a th1 immune response. alternatively, antigens targeting the cd8 and t-regulatory responses are also relevant in vl pathogenesis and worthy of being included in a preventive human vaccine. we assessed in active and cured patients and vl asymptomatic subjects the clinical signs and cytokine responses to the leishmania donovani nucleoside hydrolase nh36 antigen and its ...201728321221
diagnostic accuracy of rklo8 versus rk26 elisas for screening of canine visceral leishmaniasis.canine visceral leishmaniasis (cvl) represents an important public health issue. despite numerous diagnostic tests available, cvl diagnosis still needs to be improved to achieve a more accurate detection rate. recently, rklo8, a new antigenic protein of sudanese leishmania donovani, was studied for the first time in diagnosis of human visceral leishmaniasis (hvl) and showed good performance. the present study aimed to evaluate serum reactivity to rkl08 and the reference antigen rk26, and to comp ...201727876645
spatiotemporal uncoupling of microrna-mediated translational repression and target rna degradation controls micrornp recycling in mammalian cells.microrna (mirna)-mediated repression controls expression of more than half of protein-coding genes in metazoan animals. translation repression is associated with target mrna degradation initiated by decapping and deadenylation of the repressed mrnas. earlier evidence suggests the endoplasmic reticulum (er) as the site where micrornps (mirnps) interact with their targets before translation repression sets in, but the subcellular location of subsequent degradation of mirna-repressed messages is la ...201727895152
pharmacological inhibition of p110δ subunit of pi3k confers protection against experimental leishmaniasis.this study aimed to evaluate the immuno-prophylactic and -therapeutic effect of p110δ-specific pharmacological inhibitors (cal-101 and ic87114), either alone or in combination with amphotericin b, against experimental cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl).201727999013
characterization of ciliobrevin a mediated dynein atpase inhibition on flagellar motility of leishmania donovani.axonemal dyneins are members of aaa+ proteins involved in force generation and are responsible for flagellar motility in eukaryotes. in this study, we characterized the effects of ciliobrevin a (cba), a dynein atpase inhibitor, on flagella driven motility of the protozoan parasite leishmania donovani. using fast-capture video microscopy, we observed that cba decreased flagellar beat frequency of swimming parasites in a concentration-dependent manner. beat frequency of live and reactivated l. don ...201728389272
immuno-informatics based approaches to identify cd8+ t cell epitopes within the leishmania donovani 3-ectonucleotidase in cured visceral leishmaniasis subjects.leishmaniases are vector-borne diseases for which no vaccine exists. these diseases are caused by the leishmania species complex. activation of the cd8(+) t cell is crucial for protection against intracellular pathogens, and peptide antigens are attractive strategies for the precise activation of cd8(+) t in vaccine development against intracellular infections. the traditional approach to mine the epitopes is an arduous task. however, with the advent of immunoinformatics, in silico epitope predi ...201728373107
structure and biosynthesis of isatropolones, bioactive amine-scavenging fluorescent natural products from streptomyces gö66.the natural products isatropolone a-c (1-3) were reisolated from streptomyces gö66, with 1 and 3 showing potent activity against leishmania donovani. they contain a rare tropolone ring derived from a type ii polyketide biosynthesis pathway. their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates. owing to their 1,5-diketone moiety, they can react with ammoni ...201728371116
expression profiling of sudanese visceral leishmaniasis patients pre- and post-treatment with sodium stibogluconate.visceral leishmaniasis (vl) in sudan caused by leishmania donovani is fatal in susceptible individuals if untreated. treatment with sodium stibogluconate (ssg) leads to post kala azar dermal leishmaniasis (pkdl) in 58% of patients. here affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (n=9 paired samples) pre- and post-treatment with ssg. using the bioconductor package limma, 438 genes from 28,869 post quality-control probe-sets were differentially expre ...201728370072
a systematic reconstruction and constraint-based analysis of leishmania donovani metabolic network: identification of potential antileishmanial drug targets.visceral leishmaniasis, a lethal parasitic disease, is caused by the protozoan parasite leishmania donovani. the absence of an effective vaccine, drug toxicity and parasite resistance necessitates the identification of novel drug targets. reconstruction of genome-scale metabolic models and their simulation has been established as an important tool for systems-level understanding of a microorganism's metabolism. in this work, amalgamating the tools and techniques of computational systems biology ...201728367572
anti-leishmanial and cytotoxic activities of amino acid-triazole hybrids: synthesis, biological evaluation, molecular docking and in silico physico-chemical properties.according to who, leishmaniasis is a major tropical disease, ranking second after malaria. significant efforts have been therefore invested into finding potent inhibitors for the treatment. in this work, eighteen novel 1,2,3-triazoles appended with l-amino acid (phe/pro/trp) tail were synthesized via azide-alkyne click chemistry with moderate to good yield, and evaluated for their anti-leishmanial activity against promastigote form of leishmania donovani (dd8 strain). among all, compounds 40, 43 ...201728359789
nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.visceral leishmaniasis (vl) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus leishmania. most of the therapeutics for vl are toxic, expensive, or ineffective. sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. association of artemisinin with liposome is a desirable str ...201728356736
biologically-guided isolation of leishmanicidal secondary metabolites from euphorbia peplus l.leishmaniasis is a worldwide health problem, highly endemic in developing countries. moreover, the severe side effects and the reported drug resistance make it an urgent need to search for effective drugs that can replace or supplement those currently used. in a research program designed to investigate the antileishmanial activity of plants collected from the egyptian flora, twenty extracts from fifteen plants growing in egypt have been investigated for in vitro leishmanicidal activity against l ...201728344474
development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of leishmania infection.leishmaniasis is a spectrum of diseases with great relevance to public health. conventional diagnostic methods are time consuming, needing trained personnel. a robust, rapid and cost effective diagnostic test is warranted for on-time diagnosis and field application.201728335752
increased transmissibility of leishmania donovani from the mammalian host to vector sand flies after multiple exposures to sand fly bites.patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of leishmania donovani. the role of the blood or skin as a source of infection to sand flies remains unclear, and the possible effect of multiple exposures to fly bites on transmissibility has not been addressed.201728329329
domestic dogs as reservoir hosts for leishmania donovani in the southernmost western ghats in india.the peripheral blood samples from domestic dogs (n=47) and wild rats (n=25) in the kani tribe settlements, located southernmost part of the western ghats, thiruvananthapuram district, kerala, india were examined for leishmania infection. this area is known for cases of leishmaniasis with cutaneous manifestations and sandfly abundance. the tribes domesticate dogs to protect them from untoward activities of wild animals. leishmania donovani parasite dna was detected only from 6.4% (n=3) of the blo ...201728327413
leishmania donovani resistant to ambisome or miltefosine exacerbates cd58 expression on nk cells and promotes trans-membrane migration in association with cd2.visceral leishmaniasis (vl) is a disease that is associated with compromised immunity and drug un-responsiveness as well as with the emergence of drug resistance in leishmania donovani (ld). ld down-modulates cellular immunity by manipulating signaling agents, including a higher expression of the adhesion molecule cd58. the expression of cd58 and cd2 on natural killer (nk) cells facilitates intercellular adhesion and signaling. the influence of drug-resistant ld on the expression of cd58 and cd2 ...201728324803
identification of novel inhibitors of leishmania donovani γ-glutamylcysteine synthetase using structure-based virtual screening, docking, molecular dynamics simulation, and in vitro studies.trypansomatids maintain their redox balance by the trypanothione-based redox system, enzymes of which exhibit differences from mammalian homologues. γ-glutamylcysteine synthetase (gcs) is an essential enzyme in this pathway that performs the first and rate-limiting step. l-buthionine-(s,r)-sulfoximine (bso), a specific inhibitor of gcs, induces toxicity in hosts infected with trypanosoma brucei, underlining the need for novel gcs inhibitors. the present study reports identification of leishmania ...201728322559
antileishmanial and immunomodulatory potential of ocimumsanctum linn. and cocosnucifera linn. in murine visceral leishmaniasis.the role of immunomodulation in the therapeutic treatment of visceral leishmaniasis has gained eminence in view of moderate to severe drawbacks of the currently available drugs like toxicity, drug resistance and prohibitive costs. the potential for modulation of the immune system of many herbal plants can be tapped to address these problems. we conducted the present research study to investigate the antileishmanial and immunomodulatory effects of ocimum sanctum linn. and cocos nucifera linn. dur ...201728316391
identification and characterization of mirnas in response to leishmania donovani infection: delineation of their roles in macrophage dysfunction.the outcome of leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. micro rnas (mirnas) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding rna gene products, described to participate in the regulation of almost every cellular process investig ...201728303124
deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating amphotericin b resistance and survival of leishmania donovani under oxidative stress.leishmania donovani is the causative organism of the neglected human disease known as visceral leishmaniasis which is often fatal, if left untreated. the cysteine biosynthesis pathway of leishmania may serve as a potential drug target because it is different from human host and regulates downstream components of redox metabolism of the parasites; essential for their survival, pathogenicity and drug resistance. however, despite the apparent dependency of redox metabolism of cysteine biosynthesis ...201728288415
clinico-epidemiological patterns of cutaneous leishmaniasis patients attending the anuradhapura teaching hospital, sri lanka.cutaneous leishmaniasis (cl) caused by leishmania donovani is an endemic vector-borne disease in sri lanka. over 2,500 cases have been reported since 2000 and the number of cl cases has dramatically increased annually. total 57 clinically suspected cl patients attending the dermatology clinic in anuradhapura teaching hospital were recruited from january to june 2015. slit skin smears and skin biopsies were taken from each of the subjects. clinical and epidemiological data were obtained using int ...201728285499
leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages.protozoa of the genus leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. the search for leishmania effectors that support macrophage infection is a focus of significant interest. one such candidate is leishmania chaperonin 10 (cpn10) which is secreted in exosomes and may have immunosuppressive properties. here, we report for the first time that leishmania cpn10 localizes to the cytosol of infected macrophages. next, we generated two ...201728283754
revisiting previously investigated plants: a molecular networking-based study of geissospermum laeve.three new monoterpene indole alkaloids (1-3) have been isolated from the bark of geissospermum laeve, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). the structures of 1-3 were elucidated by analysis of their hrms and nmr spectroscopic data. the absolute configuration of geissolaevine (1) was deduced from the comparison of experimental and theoretically calculated ecd spectra. the isolation workflow was guided by a molecular networking-based dere ...201728282127
evaluation of caax prenyl protease ii of leishmania donovani as potential drug target: infectivity and growth of the parasite is significantly lowered after the gene knockout.prenylation pathway is responsible for post translational modification of various signal proteins, including proteins of ras superfamily. caax prenyl proteases are known to be key players in prenylation pathway. in the current study, we have evaluated caax prenyl protease ii as a possible drug target against leishmania donovani parasite, the causative agent of visceral leishmaniasis. gene knockout strategy was employed to target caax prenyl protease ii and subsequent effects were studied. caax p ...201728279761
methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in leishmania donovani.we investigate the role of methionine aminopeptidase 2 (map2) in miltefosine induced programmed cell death (pcd) in promastigote form of l. donovani. we report that tnp-470, an inhibitor of map2, inhibits programmed cell death in miltefosine treated promastigotes. it inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal dna fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium i ...201728273904
new developments in probing and targeting protein acylation in malaria, leishmaniasis and african sleeping sickness.infections by protozoan parasites, such as plasmodium falciparum or leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. the increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. post-translational modifications (ptms) are important modulators of ...201728270257
role of leishmanial acidocalcisomal pyrophosphatase in the camp homeostasis in phagolysosome conditions required for intra-macrophage survival.exposure of leishmania donovani to macrophage phagolysosome conditions (pc) (37°c and ph 5.5) led to increased intracellular camp and camp-mediated responses, which help in intra-macrophage survival pre-requisite for infectivity. in the absence of typical orthologs for g-proteins and g-protein coupled receptors, we sought to study the precise mechanisms for positive modulation of camp production during exposure to pc. amongst two promastigote-stage specific membrane bound receptor adenylate cycl ...201728268199
integrating genomics and proteomics permits identification of immunodominant antigens associated with drug resistance in human visceral leishmaniasis in india.resistance of human pathogens like leishmania to drugs is a growing concern where the multidrug-resistant phenotype renders chemotherapy ineffective. the acquired resistance of leishmania to antimony has promoted intense research on the mechanisms involved but the question has not been resolved yet. in this study we have explored host-pathogen- drug interactions leading to identification of pharmacological determinants of host macrophages that resist the sodium antimony gluconate (sag) mediated ...201728263760
single locus genotyping to track leishmania donovani in the indian subcontinent: application in nepal.we designed a straightforward method for discriminating circulating leishmania populations in the indian subcontinent (isc). research on transmission dynamics of visceral leishmaniasis (vl, or kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the isc. vl in bangladesh, india, and nepal is caused by genetically homogeneous populations of leishmania donovani parasites, transmitted by female sandflies. classical methods to study diversity of ...201728249021
glycyrrhizic acid attenuates growth of leishmania donovani by depleting ergosterol levels.in the present study, glycyrrhizic acid (ga) the main component of glycyrrhiza glabra was evaluated for its efficacy as antileishmanial agent and its mode of action explored. ga inhibits promastigotes and intracellular amastigotes in a dose dependent manner at an ic50 value of 34 ± 3.0 μm and 20 ± 4.2 μm respectively. ga was non-toxic against thp-1 macrophage host cell line. ga was found to inhibit recombinant leishmania donovani hmg-coa reductase (ldhmgr) enzyme at the half-maximum inhibitory c ...201728242356
synthesis and antitrypanosomal activities of novel pyridylchalcones.a library of novel pyridylchalcones were synthesised and screened against trypanosoma brucei rhodesiense. eight were shown to have good activity with the most potent 8 having an ic50 value of 0.29 μm. cytotoxicity testing with human kb cells showed a good selectivity profile for this compound with a selectivity index of 47. little activity was seen when the library was tested against leishmania donovani. in conclusion, pyridylchalcones are promising leads in the development of novel compounds fo ...201728189085
cloning, characterization and subcellular localization of nuclear lim interactor interacting factor gene from leishmania donovani.lim domains are zinc-binding motifs that mediate protein-protein interactions and are found in a wide variety of cytoplasmic and nuclear proteins. the nuclear lim domain family members have a number of different functions including transcription factors, gene regulation, cell fate determination, organization of the cytoskeleton and tumour formation exerting their function through various lim domain interacting protein partners/cofactors. nuclear lim domain interacting proteins/factors have not b ...201728188871
putative drug and vaccine target identification in leishmania donovani membrane proteins using naïve bayes probabilistic classifier.predicting the role of protein is one of the most challenging problems. there are few approaches available for the prediction of role of unknown protein in terms of drug target or vaccine candidate. we propose here naïve bayes probabilistic classifier, a promising method for reliable predictions. this method is tested on the proteins identified in our mass spectrometry based membrane protemics study of leishmania donovani parasite that causes a fatal disease (visceral leishmaniasis) in humans al ...201728182549
glucose-6-phosphate dehydrogenase and trypanothione reductase interaction protects leishmania donovani from metalloid mediated oxidative stress.exploration of metabolons as viable drug target is rare in kinetoplastid biology. here we present a novel protein-protein interaction among glucose-6-phosphate dehydrogenase (ldg6pdh) and trypanothione reductase (ldtryr) of leishmania donovani displaying interconnection between central glucose metabolism and thiol metabolism of this parasite. digitonin fractionation patterns observed through immunoblotting indicated localisation of both ldg6pdh and ldtryr in cytosol. in-silico and in-vitro inter ...201728179112
copper salisylaldoxime (cusal) imparts protective efficacy against visceral leishmaniasis by targeting leishmania donovani topoisomerase ib.in vitro and in vivo anti-leishmanial efficacy of copper salisylaldoxime (cusal), a transition metal complex, was evaluated and the underlying mechanism was studied. in vitro studies revealed that 30 μm of cusal causes 96% reduction in parasite burden in infected macrophages. cusal is least toxic in host cells. a dose of 5 mg/kg bodyweight per mice on alternate days (5 doses) gives ∼97% protection in both liver and spleen. moreover, cusal potentially inhibits the catalytic activity of ldtopils a ...201728174102
evaluation of the antileishmanial potency, toxicity and phytochemical constituents of methanol bark extract of sterculia villosa.visceral leishmaniasis is a protozoan disease caused by leishmania donovani parasite. the genus sterculia (malvaceae) possesses ethnobotanical potential against this protozoan infection.201728173714
apoptosis-like cell death in leishmania donovani treated with kalsometm10, a new liposomal amphotericin b.the present study aimed to elucidate the cell death mechanism in leishmania donovani upon treatment with kalsometm10, a new liposomal amphotericin b.201728170432
efficacy of protease inhibitor from marine streptomyces sp. vitbvk2 against leishmania donovani - an in vitro study.in the present study the leishmanicidal effect of potential protease inhibitor producing marine actinobacterial isolate has been investigated against leishmania donovani, the causative agent of visceral leishmaniasis. among 89 marine actinobacteria isolated from a salt pan in kanyakumari, only one isolate (bvk2) showed 97% of protease inhibition activity against trypsin. moderate to high protease inhibitor activity was shown by isolate bvk2 on proteinase (30%) and chymotrypsin (85%). in optimiza ...201728167209
changes in lipid and fatty acid composition during intramacrophagic transformation of leishmania donovani complex promastigotes into amastigotes.leishmania sp., are trypanosomatid parasites that are phagocytized by human and animal macrophages. transformation from the vector promastigote stage to the intracellular amastigote host cell stage is mandatory, since development in the host depends on the internalization of the parasite. we identified and analyzed the lipids involved in the promastigote to amastigote transformation process in the leishmania donovani complex. four lipid classes, phospholipids, free fatty acids, triglycerides and ...201728161835
withania somnifera chemotype nmitli 101r significantly increases the efficacy of antileishmanial drugs by generating strong ifn-γ and il-12 mediated immune responses in leishmania donovani infected hamsters.withania somnifera (l.) dunal (solanaceae), commonly known as ashwagandha, is one of the most important medicinal plant in the traditional indian medical systems. pharmacological studies have established that root extracts of w. somnifera contain several bioactive constituents called withanolides. the plant has long been used for its several beneficial properties and recently as an immunomodulator.201728160866
synthesis of 16 new hybrids from tetrahydropyrans derivatives and morita-baylis-hillman adducts: in vitro screening against leishmania donovani.leishmaniases are a group of neglected tropical diseases (ntds) caused by protozoan parasites from >20 leishmania species. visceral leishmaniasis (vl), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. the morita-baylis-hillman adducts (mbhas) are being explored as drug candidates against several diseases, one of them being leishmaniasis. we present here the design, synthesis and in vitro screening against leishmania dono ...201728146095
transcriptional profiling in experimental visceral leishmaniasis reveals a broad splenic inflammatory environment that conditions macrophages toward a disease-promoting phenotype.visceral leishmaniasis (vl), caused by the intracellular protozoan leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. progressive disease is considered to be due to impaired effector t cell function and/or failure of macrophages to be activated to kill the intracellular parasite. in previous studies, we used the syrian hamster (mesocricetus auratus) as a model because it mimics the pro ...201728141856
laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from india.miltefosine unresponsive and relapse cases of visceral leishmaniasis (vl) are increasingly being reported. however, there has been no laboratory confirmed reports of miltefosine resistance in vl. here, we report two laboratory confirmed cases of vl from india.201728137296
genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite leishmania.5-hydroxymethyluracil (5hmu) is a thymine base modification found in the genomes of a diverse range of organisms. to explore the functional importance of 5hmu, we develop a method for the genome-wide mapping of 5hmu-modified loci based on a chemical tagging strategy for the hydroxymethyl group.201728137275
comprehensive identification of mrna-binding proteins of leishmania donovani by interactome capture.leishmania are unicellular eukaryotes responsible for leishmaniasis in humans. like other trypanosomatids, leishmania regulate protein coding gene expression almost exclusively at the post-transcriptional level with the help of rna binding proteins (rbps). due to the presence of polycystronic transcription units, leishmania do not regulate rna polymerase ii-dependent transcription initiation. recent evidence suggests that the main control points in gene expression are mrna degradation and transl ...201728135300
antiprotozoal glutathione derivatives with flagellar membrane binding activity against t. brucei rhodesiense.a new series of n-substituted s-(2,4-dinitrophenyl)glutathione dibutyl diesters were synthesized to improve in vitro anti-protozoal activity against the pathogenic parasites trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the results obtained indicate that n-substituents enhance the inhibitory properties of glutathione diesters whilst showing reduced toxicity against kb cells as in the cases of compounds 5, 9, 10, 16, 18 and 19. we suggest that the interaction of n-sub ...201728131508
indian erythrodermic postkala-azar dermal leishmaniasis.postkala-azar dermal leishmaniasis (pkdl) is a complication of kala-azar or visceral leishmaniasis and is caused by leishmania donovani. we describe an indian male patient with the rarer erythrodermic form of pkdl and multiple unusual skin lesions viz. verrucous, annular and mucosal ulceration.201728130283
optimized crispr-cas9 genome editing for leishmania and its use to target a multigene family, induce chromosomal translocation, and study dna break repair mechanisms.crispr-cas9-mediated genome editing has recently been adapted for leishmania spp. parasites, the causative agents of human leishmaniasis. we have optimized this genome-editing tool by selecting for cells with crispr-cas9 activity through cotargeting the miltefosine transporter gene; mutation of this gene leads to miltefosine resistance. this cotargeting strategy integrated into a triple guide rna (grna) expression vector was used to delete all 11 copies of the a2 multigene family; this was not p ...201728124028
exploration of new and potent lead molecules against caax prenyl protease i of leishmania donovani through pharmacophore based virtual screening approach.visceral leishmaniasis is a deadly disease left untreated in over 95% of cases. it is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anemia. it is highly endemic in the indian subcontinent. caax prenyl proteasei of leishmania donovani is one of the important targets regulating the post translational modification process. hence identifying potent drug candidate against the target is essential. this study mainly focuses on developing new and potent ...201728116998
antiprotozoal activity-based profiling of a dichloromethane extract from anthemis nobilis flowers.a dichlomethane extract of anthemis nobilis flower cones showed promising in vitro antiprotozoal activity against trypanosoma brucei rhodesiense and leishmania donovani, with ic50 values of 1.43 ± 0.50 and 1.40 ± 0.07 μg/ml, respectively. a comprehensive profiling of the most active fractions afforded 19 sesquiterpene lactones, including 15 germacranolides, two seco-sesquiterpenes, one guaianolide sesquiterpene lactone, and one cadinane acid. of these, 13 compounds were found to be new natural p ...201728116906
elimination of kala-azar from the southeast asia region.visceral leishmaniasis (vl), popularly known as kala-azar, is essentially a disease of poverty. kala-azar is caused by a parasite, leishmania donovani recent review indicates that worldwide 98 countries are endemic for kala-azar. approximately 0.2-0.4 million new vl cases occur each year worldwide. more than 90% of global vl cases occur in bangladesh, brazil, ethiopia, india, south sudan, and sudan. this trend is slowly changing due to the progress in kala-azar elimination in southeast asia, whe ...201728115678
design, synthesis and antimalarial activity of novel bis{n-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives.novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of w2 and 3d7 plasmodium falciparum strains. biological results showed good antimalarial activity with ic50 in the μm range. in attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward leishmania donovani were also investigated and revealed their selective antiplasmodial profil ...201728114821
in situ immunopathological changes in cutaneous leishmaniasis due to leishmania donovani.cutaneous leishmaniasis in sri lanka is a newly established parasitic disease caused by the usually visceralizing leishmania donovani. skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. in situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of t-helper 1 (th1) and t-helper 2 (th2) cytokines, namely interferon (ifn)-γ, inter ...201728112425
splenic cd4+ t cells in progressive visceral leishmaniasis show a mixed effector-regulatory phenotype and impair macrophage effector function through inhibitory receptor expression.visceral leishmaniasis (vl), caused by infection with the intracellular protozoan leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. the disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. control of leishmania infection is mediated by th1 (ifnγ-producing) cd4+ t cells, which activate macrophages to produce nitric oxide and kill intracellular pa ...201728103263
snapshot profiling of the antileishmanial potency of lead compounds and drug candidates against intracellular leishmania donovani amastigotes, with a focus on human-derived host cells.this study characterized the in vitro potencies of antileishmanial agents against intracellular leishmania donovani amastigotes in primary human macrophages, obtained with or without cd14-positive monocyte enrichment, phorbol 12-myristate 13-acetate (pma)-differentiated thp-1 cells, and mouse peritoneal exudate macrophages (pems). host cell-dependent potency was confirmed for pentavalent and trivalent antimony. fexinidazole was inactive against intracellular amastigotes across the host cell pane ...201728069646
assessment of formulated amodiaquine microparticles in leishmania donovani infected rats.the aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against leishmania donovani. microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. the microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. the size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mv. of t ...201728067090
immunization with leishmania donovani protein disulfide isomerase dna construct induces th1 and th17 dependent immune response and protection against experimental visceral leishmaniasis in balb/c mice.in the present study, the efficacy of leishmania donovani protein disulfide isomerase (ldpdi) as a dna vaccine was evaluated in balb/c mice. mice immunized with the ldpdi-dna construct were found to be the most immuno-reactive, as the construct induced higher t-cell proliferation. the increased t-cell proliferation was associated with a substantial rise in th1 and th17+ cd4 cell response and triggered a higher proportion of cd8+ t cells for the release of interferon-gamma along with a reduced sp ...201728064069
antileishmanial activity of pyrazolopyridine derivatives and their potential as an adjunct therapy with miltefosine.a series of pyrazolo(dihydro)pyridines was synthesized and evaluated for antileishmanial efficacy against experimental visceral leishmaniasis (vl). among all compounds, 6d and 6j exhibited better activity than miltefosine against intracellular amastigotes. compound 6j (50 mg/kg/day) was further studied against leishmania donovani/balb/c mice via the intraperitoneal route for 5 days and displayed >91 and >93% clearance of splenic and liver parasitic burden, respectively. combination treatment of ...201728059524
a chimera containing cd4+ and cd8+ t-cell epitopes of the leishmania donovani nucleoside hydrolase (nh36) optimizes cross-protection against leishmania amazonesis infection.the leishmania donovani nucleoside hydrolase (nh36) and nh a34480 of leishmania amazonensis share 93% of sequence identity. in mice, the nh36 induced protection against visceral leishmaniasis is mediated by a cd4+ t cell response against its c-terminal domain (f3). besides this cd4+ th1 response, prevention and cure of l. amazonensis infection require also additional cd8+ and regulatory t-cell responses to the nh36 n-terminal (f1 domain). we investigated if mice vaccination with f1 and f3 domain ...201728280494
perifosine mechanisms of action in leishmania species.here the mechanism by which perifosine induced cell death in leishmania donovani and leishmania amazonensis is described. the drug reduced leishmania mitochondrial membrane potential and decreased cellular atp levels while increasing phosphatidylserine externalization. perifosine did not increase membrane permeabilization. we also found that the drug inhibited the phosphorylation of akt in the parasites. these results highlight the potential use of perifosine as an alternative to miltefosine aga ...201728096161
diagnosis of visceral leishmaniasis using peripheral blood microscopy in ethiopia: a prospective phase-iii study of the diagnostic performance of different concentration techniques compared to tissue aspiration.visceral leishmaniasis (vl) is a fatal parasitic disease. unfortunately, diagnosis of vl in east africa currently relies on aspiration of tissue from the spleen or bone marrow, which is painful and potentially dangerous. we sought to determine whether peripheral blood could be used instead of invasive tissue aspirates to diagnose vl, using three parasite concentration techniques. three hundred and one consecutive people suspected of having vl were recruited. compared with microscopy of tissue as ...201727799651
biochemical and inhibition studies of glutamine synthetase from leishmania donovani.leishmaniasis is a group of tropical diseases caused by protozoan parasites of the genus leishmania. leishmania donovani is a protozoan parasite that causes visceral leishmaniasis, a fatal disease if left untreated. chemotherapy for leishmaniasis is problematic as the available drugs are toxic, costly and shows drug resistance, hence, there is a necessity to look out for the novel drug targets, chemical entities and vaccine. glutamine synthetase (gs) catalyzes the synthesis of glutamine from glu ...201728351708
expression, purification, immunogenicity and protective efficacy of a recombinant nucleoside hydrolase from leishmania donovani, a vaccine candidate for preventing cutaneous leishmaniasis.the nucleoside hydrolase gene from leishmania donovani was cloned and expressed in escherichia coli as a full length 36-kda protein (ldnh36). following lysis and extraction, the protein was purified by anion exchange and gel filtration chromatography. the purified protein had a molecular mass of approximately 36-kda and was confirmed to be >99% pure. using a nucleoside hydrolase assay, the protein was found to exhibit a km of 741 ± 246 μm. protein integrity was confirmed by lithium dodecyl sulfa ...201727773761
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 ...201726629453
synthesis and in vitro screening of 29, 30-dibromo-28-oxoallobetulin against parasitic protozoans, leishmania donovani and leishmania major.a simple synthesis and in vitro antileishmanial activity of 29,30-dibromo-28-oxoallobetulin against the parasitic protozoans, leishmania donovani and leishmania major is described. the structure of the compound is established on the basis of spectral data (ir, nmr, ms). both the antiproliferative effect and the cell cycle progression were studied.201726009654
structure-based virtual screening, molecular docking, admet and molecular simulations to develop benzoxaborole analogs as potential inhibitor against leishmania donovani trypanothione reductase.visceral leishmaniasis (vl) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and pentamidine has been reported in the vl endemic region. amphotericin b has shown potential antileishmanial activity in different formulations but its cost of treatment and associated nephrotoxicity have limited its use by affected people living in the endemic zone. to control the vl infection ...201727147242
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