Bilayer Effects of Antimalarial Compounds

• DOI: 10.1371/journal.pone.0142401
• Publication Date: 2015-11-09T13:28:00Z
• Authors: Nicole B. Ramsey; Olaf S. Andersen
• Keywords: 0303 health sciences; Protein Conformation; Science; Q; Cell Membrane; Lipid Bilayers; R; Drug Evaluation, Preclinical; Membrane Proteins; Biophysical Phenomena; Cell Line; 3. Good health; Antimalarials; 03 medical and health sciences; Spectrometry, Fluorescence; Drug Discovery; Medicine; Humans; Research Article

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. Among the Malaria Box compounds tested, four compounds altered membrane properties (p< 0.05); MMV007384 stood out as a potent bilayer-perturbing compound that is toxic in many cell-based assays, suggesting that testing for membrane perturbation could help identify toxic compounds. In any case, MMV007384 should be approached with caution, if at all.