| 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 gramicidinbased 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. © 2015 Ramsey, Andersen.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: |
controlled study; unclassified drug; human cell; drug potency; drug effect; membrane protein; conformational transition; antimalarial agent; drug determination; fluorescence analysis; lipid bilayer; gramicidin; cytotoxicity test; human; article; ec50; 2 [[1 (2,4 dimethoxyphenyl) 1h imidazol 2 yl]sulfanyl] n (2,5 dimethylphenyl)acetamide; 5,5' methylenebis [2 (4 methoxyphenyl) 1h benzimidazole]; n [4 [(4 ethyl 1 piperazinyl)methyl]phenyl] 1h pyrrolo[3,2 h]quinoline 2 carboxamide; n [4 [(4 methyl 1 piperidinyl)methyl]phenyl] 1h pyrrolo[3,2 h]quinoline 2 carboxamide
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