ANTIMALARIAL COMPOUNDS AS ANTAGONISTS OF ADENOSINE

Redox systems as conduits for antimalarial compounds.

Sir, At the turn of the nineteenth century, Ehrlich focused on the selective staining of malaria-infected cells over noninfected cells, with methylene blue and acridine orange. On reviewing this information, two simple questions arose: why do these compounds selectively target parasite infected cells and can this information be used against the parasite? We propose the following: methylene blue...

Flavonoids as antagonists at A1 adenosine receptors.

This study aimed to investigate the potential for flavonoid action at A(1) adenosine receptors in vitro. In a radioligand binding assay for A(1) adenosine receptor occupancy in particulate preparations from guinea-pig cerebral cortex, flavonoids competed in concentration-dependent manners with Hill slopes typically not different from unity. Of the flavonoids tested, quercetin showed highest aff...

Bilayer Effects of Antimalarial Compounds

Because of the perpetual development of resistance to current therapies for malaria, the Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process. We tested the 80 most potent compounds from the box for bilayer-mediated effects on membrane protein conformational changes (a measure of likely toxicity) in a gramicidin-based stopped flow fluorescence assay...

Adenosine Receptor Antagonists(1)

Antimalarial activities of aminooxy compounds.

Twenty-three aminooxy compounds have been examined for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum in vitro. Eight of these compounds were found to have 50% inhibitory concentrations less than 10 microM, with the best drugs being canaline (the aminooxy analogue of ornithine) and CGP51905A at 297 +/- 23.6 nM and 242 +/- 18.8 nM, respectively. Canaline was al...