Search results for "Plasmodium Falciparum"

In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents

2012

Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum , Leishmania infantum , Trypanosoma brucei , and Trypanosoma cruzi , resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds

Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization an…

2016

The synthesis and characterization of twenty new pentamethylcyclopentadienyl-rhodium and iridium complexes containing N^N and N^O-chelating chloroquine analogue ligands are described. The in vitro antimalarial activity of the new ligands as well as the complexes was evaluated against the chloroquine sensitive (CQS) NF54 and the chloroquine resistant (CQR) Dd2 strains of Plasmodium falciparum. The antimalarial activity was found to be good to moderate; although all complexes are less active than artesunate, some of the ligands and complexes showed better activity than chloroquine (CQ). In particular, rhodium complexes were found to be considerably more active than iridium complexes against t…

Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.

2010

Apicomplexan parasites encompass several human- and animal-pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin-dependent kinases (CDKs) are key molecules in cell-cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK-like proteins, of which one—E. tenella CDK-related kinase 2 (EtCRK2)—has already been charact…

2019

Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2–13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 μg/mL. The is…

Discovery of new antimalarial compounds by use of molecular connectivity techniques.

1999

Abstract Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity functions were used to select several potentially suitable drugs which were tested for antimalarial properties by use of an in-vitro micro test which estimates parasite growth by measurement of incorporation of [3H]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were performed with Plasmodium falciparum passou and 3CD7 strains, for which the IC50 values (doses resulting in 50% inhibition) were 320 and 400 ng mL−1 respectively. These results are comparable with those obtained for quinine chlorhydrate (IC50…

Dioncophyllines C2, D2, and F and related naphthylisoquinoline alkaloids from the Congolese liana Ancistrocladus ileboensis with potent activities ag…

2017

Dioncophylline F (1), the first 5,8'-coupled dioncophyllaceous alkaloid (i.e., lacking an oxygen function at C-6 and possessing an R-configuration at C-3), was isolated from the recently described Congolese liana Ancistrocladus ileboensis. Two further, likewise Dioncophyllaceae-type, alkaloids, the dioncophyllines C2 (2) and D2 (3), were identified, along with the Ancistrocladaceae-type compound ancistrocladisine B (4), which is oxygenated at C-6 and S-configured at C-3. The structures of the new compounds were determined by spectroscopic, chemical, and chiroptical methods. The stereostructure of 1 was further confirmed by total synthesis. As a consequence of the lack of a methyl group orth…

Prenylated Flavonoids from the Roots of Tephrosia rhodesica

2020

Five new compounds—rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)—along with 16 known secondary metabolites, were isolated from the CH2Cl2–CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2–5, 9, 15, and 21 showed activity (100% at 10 μg and IC50 = 5–15 μM) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. peerReviewed

Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C

2014

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad ran…

Aplicación de la topología molecular a la predicción de la actividad antimalárica de análogos de la 4-anilinoquinolina

2021

La malaria es una enfermedad parasitaria causada por protozoos del género Plasmodium y transmitida por vectores del género Anopheles . En 2019 esta enfermedad se cobró la vida de más de 400.000 personas, de las cuales un 94 % se concentraban en la región de África. Uno de los principales problemas en el control de la malaria es la aparición de resistencias frente a los diferentes fármacos que existen, es por ello que es necesario el desarrollo de alternativas antimaláricas eficaces. En este estudio se ha aplicado la topología molecular a una serie de compuestos análogos de la 4-anilinoquinolina con actividad inhibitoria de la proliferación de 3 cepas de Plasmodium falciparum, una sensibl…

New active drugs against liver stages of Plasmodium predicted by molecular topology.

2008

ABSTRACT We conducted a quantitative structure-activity relationship (QSAR) study based on a database of 127 compounds previously tested against the liver stage of Plasmodium yoelii in order to develop a model capable of predicting the in vitro antimalarial activities of new compounds. Topological indices were used as structural descriptors, and their relation to antimalarial activity was determined by using linear discriminant analysis. A topological model consisting of two discriminant functions was created. The first function discriminated between active and inactive compounds, and the second identified the most active among the active compounds. The model was then applied sequentially t…