Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite.

Dolichols are isoprenoid end-products of the mevalonate and 2-methyl-D-erythritol-4-phosphate pathways. The synthesis of dolichols is initiated with the addition of several molecules of isopentenyl diphosphate to farnesyl diphosphate. This reaction is catalyzed by a -prenyltransferase and leads to the formation of polyprenyl diphosphate.

Malaria Box-Inspired Discovery of -Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.

Virtual ligand screening of a publicly available database of antimalarial hits using a pharmacophore derived from antimalarial MMV008138 identified TCMDC-140230, a tetrahydro-β-carboline amide, as worthy of exploration. All four stereoisomers of this structure were synthesized, but none potently inhibited growth of the malaria parasite . Interestingly, , a minor byproduct of these syntheses, proved to be potent against and was orally efficacious (40 mg/kg) in an mouse model of malaria.

Enantiopure Benzofuran-2-carboxamides of 1-Aryltetrahydro-β-carbolines Are Potent Antimalarials .

The tetrahydro-β-carboline scaffold has proven fertile ground for the discovery of antimalarial agents (e.g., MMV008138 () and cipargamin ()).

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect.

We conducted a preregistered multilaboratory project ( = 36; = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the . Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( = 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.