02384nas a2200217   4500008004100000022001400041245013500055210006900190260009900259300001200358490000600370520152100376653001201897653002301909653001501932100002001947700001901967700002401986700003102010856012502041       2013                        eng d  a1995-764500aIsolation, fractionation and evaluation of the antiplasmodial properties of Phyllanthus niruri resident in its chloroform fraction0 aIsolation fractionation and evaluation of the antiplasmodial pro  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLANDbELSEVIER SCI LTDcMAR  a169-1750 v63 a<p>Objective: To investigate the antiplasmodial activity of Phyllanthus niruri (P. niruri) methanol extract (ME) and its fractions in mice. Methods: P. niruri methanol extract and its chloroform, ethanol and aqueous portions were tested against chloroquine-sensitive Plasmodium berghei berghei. in early, established mid repository models of infection using Knight and Peter's 4-day suppressive model, Ryley and Peters curative model and Peters prophylactic model respectively. Results: Chemosuppression of parasitaemia (37.65%-50.53 %) was elicited by 100-400 mg/kg (b.w.) of ME. At doses of 100 mg/kg b.w., the chloroform fraction (F1) significantly (P&lt;0.01) suppressed parasitaemia by 85.29%, while ethanol and aqueous fractions (F2 and F3, respectively) elicited 67.06% and 51.18% chemosuppression. The most active fraction, F1 was selected for further antiplasmodial screening. In established infection, ME reduced parasitaemia (15.81%-62.96%) while F1 significantly (P&lt;0.01) reduced parasitaemia (44.36%-90.48%), with effects comparable to that of chloroquine (96.48%). The prophylactic antiplasmodial activity of ME (92.50% suppression) was also significant (P&lt;0.01) and was more effective than pyrimethamine (85.00%). Additionally, cell membrane integrity of non-parasitized erythrocytes incubated with 125-500 mg/mL F1 was maintained. Conclusions: These findings indicate the antiplasmodial efficacy of P. niruri methanol extract, and the localization of this effect in its chloroform fraction.</p>10amalaria10aPhyllanthus niruri10aPlasmodium1 aIfeoma, Obidike1 aSamuel, Okhale1 aItohan, Aboh, Mercy1 aAdeola, Salawu, Oluwakanyi  uhttps://library.ncl.res.in/content/isolation-fractionation-and-evaluation-antiplasmodial-properties-phyllanthus-niruri-002207nas a2200229   4500008004100000022001400041245020100055210006900256260005700325300001400382490000800396520130300404653001201707653002001719653002601739653001301765100001901778700001901797700001701816700001901833856012501852       2014                        eng d  a0932-011300aAntiplasmodial activity-aided isolation and identification of quercetin-4 `-methyl ether in chromolaena odorata leaf fraction with high activity against chloroquine-resistant plasmodium falciparum0 aAntiplasmodial activityaided isolation and identification of que  a233 SPRING ST, NEW YORK, NY 10013 USAbSPRINGERcDEC  a4415-44220 v1133 a<p>The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P&lt;0.05) suppressing infection by 99.46 % at 100 mg/kg body weight. Amongst its 13 sub-fractions (DF1-DF13), DF11 was highly active, with IC50 of 4.8 and 6.74 mu g/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 mu g/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3' tetrahydroxy-4'-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43-81.48 %) in mice at 2.5-5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.</p>10amalaria10aMedicinal plant10aPlasmodium falciparum10aToxicity1 aEzenyi, I., C.1 aSalawu, O., A.1 aKulkarni, R.1 aEmeje, Martins  uhttps://library.ncl.res.in/content/antiplasmodial-activity-aided-isolation-and-identification-quercetin-4-methyl-ether-002426nas a2200241   4500008004100000022001400041245012700055210006900182260011100251300001200362490000700374520149700381653002101878653002001899653001201919653001601931653002201947100003301969700001902002700001902021700001502040856012902055       2015                        eng d  a1386-207300aMegaMiner: a tool for lead identification through text mining using chemoinformatics tools and cloud computing environment0 aMegaMiner a tool for lead identification through text mining usi  aEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATESbBENTHAM SCIENCE PUBL LTDcJAN  a591-6030 v183 a<p>Virtual screening is an indispensable tool to cope with the massive amount of data being tossed by the high throughput omics technologies. With the objective of enhancing the automation capability of virtual screening process a robust portal termed MegaMiner has been built using the cloud computing platform wherein the user submits a text query and directly accesses the proposed lead molecules along with their drug-like, lead-like and docking scores. Textual chemical structural data representation is fraught with ambiguity in the absence of a global identifier. We have used a combination of statistical models, chemical dictionary and regular expression for building a disease specific dictionary. To demonstrate the effectiveness of this approach, a case study on malaria has been carried out in the present work. MegaMiner offered superior results compared to other text mining search engines, as established by F score analysis. A single query term `malaria' in the portlet led to retrieval of related PubMed records, protein classes, drug classes and 8000 scaffolds which were internally processed and filtered to suggest new molecules as potential anti-malarials. The results obtained were validated by docking the virtual molecules into relevant protein targets. It is hoped that MegaMiner will serve as an indispensable tool for not only identifying hidden relationships between various biological and chemical entities but also for building better corpus and ontologies.</p>10aChemoinformatics10acloud computing10amalaria10atext mining10avirtual screening1 aKarthikeyan, Muthukumarasamy1 aPandit, Yogesh1 aPandit, Deepak1 aVyas, Renu  uhttps://library.ncl.res.in/content/megaminer-tool-lead-identification-through-text-mining-using-chemoinformatics-tools-and-002659nas a2200277   4500008004100000022001400041245011000055210006900165260011100234300001200345490000700357520164400364653000902008653001202017653002202029653003602051653002602087653002202113653000902135100002202144700001902166700002902185700002202214700002502236856012002261       2016                        eng d  a1386-207300aVirtual screening techniques to probe the antimalarial activity of some traditionally used phytochemicals0 aVirtual screening techniques to probe the antimalarial activity   aEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATESbBENTHAM SCIENCE PUBL LTDcJUL  a572-5910 v193 a<p>Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the `rule of five' criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by `Ligplot' analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.</p>10aADME10amalaria10aMolecular docking10amolecular operating environment10aPlasmodium falciparum10avirtual screening10aweka1 aShibi, Indira, G.1 aAswathy, Lilly1 aJisha, Radhakrishnan, S.1 aMasand, Vijay, H.1 aGajbhiye, Jayant, M.  uhttps://library.ncl.res.in/content/virtual-screening-techniques-probe-antimalarial-activity-some-traditionally-used02394nas a2200253   4500008004100000245009100041210006900132260000800201300001100209490000600220520153500226653001201761653004001773653002801813653002701841100001801868700002001886700001601906700002101922700002401943700002801967700002401995856012102019       2021                        eng d00aConserved RNA binding activity of phosphatidyl inositol 5-phosphate 4-kinase (PIP4K2A)0 aConserved RNA binding activity of phosphatidyl inositol 5phospha  cMAY  a6312810 v83 aPlasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. During its life cycle, the malarial parasite Plasmodium goes through different asexual and sexual stages, in humans and mosquitoes. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In the case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that posttranscriptional regulation plays an important role in stage-specific gene expression. Translation repression of specific set of mRNA has been reported in gametocyte stages of the parasite. A conserved element present in the 3 ` UTR of some of these transcripts was identified. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K2A) was identified as the protein that associates with these RNA. We now show that the RNA binding activity of PIP4K2A is independent of its kinase activity. We also observe that PIP4K2A is imported into the parasite from the host on Plasmodium berghei and Toxoplasma gondii. The RNA binding activity of PIP4K2A seems to be conserved across species from Drosophila and C. elegans to humans, suggesting that the RNA binding activity of PIP4K may be important, and there may be host transcripts that may be regulated by PIP4K2A. These results identify a novel RNA binding role for PIP4K2A that may not only play a role in Plasmodium propagation but may also function in regulating gene expression in multicellular organisms.10amalaria10aposttranscriptional gene regulation10aRNA-protein interaction10atranslation regulation1 aBehari, Jatin1 aBorkar, Pranita1 aVindu, Arya1 aDandewad, Vishal1 aUpadrasta, Sindhuri1 aShanmugam, Dhanasekaran1 aSeshadri, Vasudevan  uhttps://library.ncl.res.in/content/conserved-rna-binding-activity-phosphatidyl-inositol-5-phosphate-4-kinase-pip4k2a02296nas a2200241   4500008004100000022001400041245011200055210006900167260000800236300001100244490000800255520148600263653001801749653002401767653001201791653001501803653001501818100002501833700001901858700002801877700001701905856013201922       2022                        eng d  a0166-685100aProfiling of metabolic alterations in mice infected with malaria parasites via high-resolution metabolomics0 aProfiling of metabolic alterations in mice infected with malaria  cNOV  a1115250 v2523 a<p>
	Background: Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood. Methods: In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA). Results: We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase. Conclusions: We have identified candidate marker metabolites that may be of relevance in the context of human malaria.</p>
10aHost response10aInfectious diseases10amalaria10ametabolite10aPlasmodium1 aChhibber-Goel, Jyoti1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aSharma, Amit  uhttps://library.ncl.res.in/content/profiling-metabolic-alterations-mice-infected-malaria-parasites-high-resolution-metabolomics03191nas a2200313   4500008004100000022001400041245011700055210006900172260000800241300001200249490000700261520213700268653002902405653002602434653001202460653002602472653001802498100002302516700002502539700002802564700002402592700002802616700002202644700002402666700001902690700001802709700002202727856012802749       2023                        eng d  a1230-282100aAntimalarial activity of anacardium occidentale leaf extracts against plasmodium falciparum transketolase (PfTK)0 aAntimalarial activity of anacardium occidentale leaf extracts ag  cDEC  a832-8410 v683 a<p>
	BackgroundAs per estimates by WHO in 2021 almost half of the world's population was at risk of malaria and &gt; 0.6 million deaths were attributed to malaria. Therefore, the present study was aimed to explore the antimalarial activity of extracts derived from the leaves of the plant Anacardium occidentale L., which has been used traditionally for the treatment of malaria. Different extracts of A.occidentale leaves were prepared and tested for their inhibitory activity against recombinant P. falciparum transketolase (rPfTK) enzyme, in vitro. Further, growth inhibitory activity against cultivated blood stage P. falciparum parasites (3D7 strain), was studied using SYBR Green fluorescence-based in vitro assays. Acute toxicity of the hydro alcoholic extracts of leaves of A. occidentale (HELA) at different concentrations was evaluated on mice and Zebra fish embryos. HELA showed 75.45 +/- 0.35% inhibitory activity against the recombinant PfTk and 99.31 +/- 0.08% growth inhibition against intra-erythrocytic stages of P. falciparum at the maximum concentration (50 mu g/ml) with IC50 of 4.17 +/- 0.22 mu g/ml. The toxicity test results showed that the heartbeat, somite formation, tail detachment and hatching of embryos were not affected when Zebra fish embryos were treated with 0.1 to 10 mu g/ml of the extract. However, at higher concentrations of the extract, at 48 h (1000 mu g/ml) and 96 h (100 mu g/ml and 1000 mu g/ml, respectively) there was no heartbeat in the fish embryos. In the acute oral toxicity tests performed on mice, the extract showed no toxicity up to 300 mg/kg body weight in mice.ConclusionThe hydro-alcoholic extract of leaves of A. occidentale L. showed potent antimalarial activity against blood stage P. falciparum. Based on the observed inhibitory activity on the transketolase enzyme of P. falciparum it is likely that this enzyme is the target for the development of bioactive molecules present in the plant extracts. The promising anti-malarial activity of purified compounds from leaves of A. occidentale needs to be further explored for development of new anti-malarial therapy.</p>
10aAnacardium occidentale L10aAntimalarial activity10amalaria10aPlasmodium falciparum10aTransketolase1 aKaushik, Meenakshi1 aHoti, Sugeerappa, L.1 aSaxena, Jitendra, Kumar1 aHingamire, Tejashri1 aShanmugam, Dhanasekaran1 aJoshi, Rajesh, K.1 aMetgud, Sharada, C.1 aUngar, Banappa1 aSingh, Ishwar1 aHegde, Harsha, V.  uhttps://library.ncl.res.in/content/antimalarial-activity-anacardium-occidentale-leaf-extracts-against-plasmodium-falciparum03461nas a2200301   4500008004100000022001400041245012200055210006900177260000800246300001200254490000700266520249900273653002002772653001202792653002002804653001802824653001202842100002102854700001902875700001902894700001702913700002102930700002202951700001602973700001702989700002803006856012503034       2026                        eng d  a2328-895700aTargeted genomic surveillance unveils genetic variations linked to regional malaria drug resistance dynamics in India0 aTargeted genomic surveillance unveils genetic variations linked   cMAR  aofag1060 v133 a<p>
	Background India has made substantial progress in reducing Plasmodium falciparum malaria cases and has set a target to eliminate malaria by 2030. Although artemisinin-based combination therapy (ACT) treatment remains effective, tracking regional differences in genetic variants associated with antimalarial resistance is required for effective drug policy implementation.Methods We analyzed 238 P. falciparum clinical samples from 6 Indian states by sequencing 15 parasite genes associated with reduced drug effectiveness. The method involved nanopore sequencing of target gene amplicons derived from dried blood spots using a highly-sensitive PfMDR15 surveillance panel.Results India's historical policy of artesunate-sulfadoxine-pyrimethamine in central India and artemether-lumefantrine in the Northeast has shaped contrasting resistance profiles. In the Northeast, chloroquine resistance persisted at high frequency (Pfcrt K76T and CVIET haplotype; Pfaat1 S258L), alongside quintuple and sextuple Pfdhfr-Pfdhps haplotypes conferring complete sulfadoxine-pyrimethamine resistance. Central India showed variable chloroquine resistance (parasites largely retained wild-type Pfcrt) and emerging lumefantrine tolerance (Pfmdr1 Y184F, Pfaat1 S258L). Interestingly, Delhi (Central India) parasites resembled profiles from the distant Northeast, which borders South East Asia. The detection of Pfaat1 S258L, previously reported only from Africa and associated with reduced lumefantrine susceptibility, suggests convergent evolution under ACT partner-drug pressure. No WHO-validated Pfk13 artemisinin resistance mutations were detected, supporting continued efficacy of ACT.Conclusions India's resistance landscape is fragmented, with signals of expanding lumefantrine tolerance and importation or evolution of globally relevant mutations. These findings highlight the importance of integrating molecular genomic surveillance into malaria control policy to monitor and protect ACT effectiveness and advance malaria elimination. Monitoring of drug resistance associated mutations in P. falciparum parasites is critical for effective drug treatment. We have demonstrated the use of a scalable genomic surveillance protocol for tracking drug resistance linked mutations in parasite genes from clinical isolates in India. The study suggests extensive regional diversity in antimalarial resistance profiles and provides the first hint of possible emergence of lumefantrine tolerance in India.</p>
10adrug resistance10amalaria10aOxford nanopore10aP. falciparum10apfMDR151 aKhilari, Ajinkya1 aSharma, Shweta1 aBajpai, Manali1 aViswan, Anju1 aChaturvedi, Rini1 aMirdha, Bijay, R.1 aRahi, Manju1 aSharma, Amit1 aShanmugam, Dhanasekaran  uhttps://library.ncl.res.in/content/targeted-genomic-surveillance-unveils-genetic-variations-linked-regional-malaria-drug