title: Bilayer Effects of Antimalarial Compounds.
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.
authors.affiliation: Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY, United States of America.|Graduate Program in Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, NY, United States of America.
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Ramsey
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, United States of America.
authors.forename: Olaf S
authors.initials: OS
authors.lastname: Andersen
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000633:toxicity*; D055592:Biophysical Phenomena; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence
chemical_list: D000962:Antimalarials; D008051:Lipid Bilayers; D008565:Membrane Proteins