In vitro models for human malaria: targeting the liver stage.

The Plasmodium liver stage represents a vulnerable therapeutic target to prevent disease progression as the parasite resides in the liver before clinical representation caused by intraerythrocytic development. However, most antimalarial drugs target the blood stage of the parasite's life cycle, and the few drugs that target the liver stage are lethal to patients with a glucose-6-phosphate dehydrogenase deficiency. Furthermore, implementation of in vitro liver models to study and develop novel therapeutics against the liver stage of human Plasmodium species remains challenging.

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.

The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.

Galtonosides A-E: Antiproliferative and Antiplasmodial Cholestane Glycosides from .

An extract of from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC value less than 1.25 μg/mL. The two known cholestane glycosides and and the five new cholestane glycosides galtonosides A-E (-) were isolated after bioassay-directed fractionation.

Anibamine and Its Analogues: Potent Antiplasmodial Agents from .

In our continuing search for novel natural products with antiplasmodial activity, an extract of was found to have good activity, with an IC value less than 1.25 μg/mL. After bioassay-directed fractionation, the known indolizinium alkaloid anibamine () and the new indolizinium alkaloid anibamine B () were isolated as the major bioactive constituents, with antiplasmodial IC values of 0.

Metabolic dependency of chorismate in Plasmodium falciparum suggests an alternative source for the ubiquinone biosynthesis precursor.

The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P.

Antiplasmodial flavanones and a stilbene from Carpha glomerata.

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D NMR data.

Antiplasmodial alkaloids from bulbs of Amaryllis belladonna Steud.

A bioassay-guided fractionation and chemical investigation of Amaryllis belladonna Steud. bulbs resulted in the isolation and identification of the new crinane alkaloid 1,4-dihydroxy-3-methoxy powellan (1), along with the 3 known crinane alkaloids 2-4 and the two lycorane alkaloids 5-6. The structures were elucidated by interpretation of combined HR-ESIMS, CD and 2D NMR spectroscopic data.

Antiplasmodial Chromanes and Chromenes from the Monotypic Plant Species Koeberlinia spinosa.

Nine new compounds containing either a chromane or chromene ring moiety were isolated from the monotypic plant Koeberlinia spinosa. Compounds 1-4 are chromanes with all possible E and Z isomers of the isoprenoid side chain, with compound 5 a methylated derivative of 1. Compounds 6 and 7 were assigned as diastereomeric cyclized derivatives of 2 and were probably artifacts formed during the extraction or the isolation processes.

Isolation of the New Antiplasmodial Butanolide, Malleastrumolide A, from Malleastrum sp. (Meliaceae) from Madagascar.

An extract of Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC value between 2.5 and 5 μg ml .

Chemical mechanism of UDP-galactopyranose mutase from Trypanosoma cruzi: a potential drug target against Chagas' disease.

UDP-galactopyranose mutase (UGM) is a flavoenzyme that catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, the precursor of galactofuranose (Galf). Galf is found in several pathogenic organisms, including the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. Galf) is important for virulence and is not present in humans, making its biosynthetic pathway an attractive target for the development of new drugs against T.