Search results for "Plasmodium Falciparum"
showing 10 items of 56 documents
The inhibition of glycerol permeation through aquaglyceroporin-3 induced by mercury(II)
2016
Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200 ns in the presence of Hg2+ ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg2+ ions covalently bound to Cys40 leads to a collapse of the aromatic/arginine selectivity filter (ar/R SF), blocking th…
Interaction of iron(II)-heme and artemisinin with a peptide mimic of Plasmodium falciparum HRP-II
2007
Abstract The interaction of heme or heme-artemisinin adducts (heme-art) with different peptides mimicking repeat sequences of the Histidine-Rich-Protein-II of Plasmodium falciparum (PfHRP-II) was investigated. The pseudo-first order rate constants of the coordination of heme or heme-art onto a histidine rich peptide, used as a mimic of PfHRP-II putative heme binding sequence, are of the same order of magnitude, namely 42 and 14 s −1 , respectively. Despite the intrinsic reactivity of the carbonyl at C10 of heme-art toward a hydroxyl function, a peptide containing a serine or threonine residue does not readily react with heme-art adducts. Therefore, a much higher affinity of heme-art compare…
Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation.
2012
Abstract Severe Plasmodium falciparum malaria evolves through the interplay among capillary sequestration of parasitized erythrocytes, deregulated inflammatory responses, and hemostasis dysfunction. After rupture, each parasitized erythrocyte releases not only infective merozoites, but also the digestive vacuole (DV), a membrane-bounded organelle containing the malaria pigment hemozoin. In the present study, we report that the intact organelle, but not isolated hemozoin, dually activates the alternative complement and the intrinsic clotting pathway. Procoagulant activity is destroyed by phospholipase C treatment, indicating a critical role of phospholipid head groups exposed at the DV surfa…
New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane…
2015
Abstract In our ongoing search for highly active hybrid molecules exceeding their parent compounds in anticancer, antimalaria as well as antiviral activity and being an alternative to the standard drugs, we present the synthesis and biological investigations of 2nd generation 1,2,4-trioxane-ferrocene hybrids. In vitro tests against the CCRF-CEM leukemia cell line revealed di-1,2,4-trioxane-ferrocene hybrid 7 as the most active compound (IC50 of 0.01 μM). Regarding the activity against the multidrug resistant subline CEM/ADR5000, 1,2,4-trioxane-ferrocene hybrid 5 showed a remarkable activity (IC50 of 0.53 μM). Contrary to the antimalaria activity of hybrids 4–8 against Plasmodium falciparum …
High-throughput screening with the Eimeria tenella CDC2-related kinase2/cyclin complex EtCRK2/EtCYC3a
2012
The poultry disease coccidiosis, caused by infection with Eimeria spp. apicomplexan parasites, is responsible for enormous economic losses to the global poultry industry. The rapid increase of resistance to therapeutic agents, as well as the expense of vaccination with live attenuated vaccines, requires the development of new effective treatments for coccidiosis. Because of their key regulatory function in the eukaryotic cell cycle, cyclin-dependent kinases (CDKs) are prominent drug targets. The Eimeria tenella CDC2-related kinase 2 (EtCRK2) is a validated drug target that can be activated in vitro by the CDK activator XlRINGO (Xenopus laevis rapid inducer of G2/M progression in oocytes). B…
Secoiridoids and Iridoids from Morinda asteroscepa
2020
The new 2,3-secoiridoids morisecoiridoic acids A (1) and B (2), the new iridoid 8-acetoxyepishanzilactone (3), and four additional known iridoids (4–7) were isolated from the leaf and stem bark methanol extracts of Morinda asteroscepa using chromatographic methods. The structure of shanzilactone (4) was revised. The purified metabolites were identified using NMR spectroscopic and mass spectrometric techniques, with the absolute configuration of 1 having been established by single-crystal X-ray diffraction analysis. The crude leaf extract (10 μg/mL) and compounds 1–3 and 5 (10 μM) showed mild antiplasmodial activities against the chloroquine-sensitive malaria parasite Plasmodium falciparum (…
Synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities.
2015
Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. The new compounds were tested for their activities against one strain of the causative organism of Malaria tropica, Plasmodium falciparum K1, which is resistant against chloroquine and pyrimethamine. In addition, their cytotoxicity and their activity against the pathogen of the East African form of sleeping sickness, Trypanosoma brucei rhodesiense, were investigated. Structure-activity relationships are discussed considering data of readily prepared compounds. For the first time, a distinct in vivo activity was observed against Plasmodium berghei in a mouse model. The active compound was further investigated.
Acute Parvovirus B19 Infection and Anemia duringPlasmodium falciparumMalaria
2002
Subacute Malaria Due toPlasmodium falciparumand the Role of Polymerase Chain Reaction
2001
Application of molecular topology to the prediction of the antimalarial activity of a group of uracil-based acyclic and deoxyuridine compounds.
2008
A topological-mathematical model has been arranged to search for new derivatives of deoxyuridine and related compounds acting as antimalarials against Plasmodium falciparum. By using linear discriminant and multilinear regression analysis a model with two functions was capable to predict adequately the IC(50) for each compound of the training and test series. After carrying out a virtual screening based upon such a model, new structures potentially active against P. falciparum are proposed.