Title | Bilayer Effects of Antimalarial Compounds. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Ramsey NB, Andersen OS |
Journal | PLoS One |
Volume | 10 |
Issue | 11 |
Pagination | e0142401 |
Date Published | 2015 |
ISSN | 1932-6203 |
Keywords | Antimalarials, Biophysical Phenomena, Cell Line, Cell Membrane, Drug Discovery, Drug Evaluation, Preclinical, Humans, Lipid Bilayers, Membrane Proteins, Protein Conformation, Spectrometry, Fluorescence |
Abstract | 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. |
DOI | 10.1371/journal.pone.0142401 |
Alternate Journal | PLoS ONE |
PubMed ID | 26551613 |
PubMed Central ID | PMC4638347 |
Grant List | GM021342 / GM / NIGMS NIH HHS / United States T32GM007739 / GM / NIGMS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 GM021342 / GM / NIGMS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm