Membrane Cholesterol Modulates Superwarfarin Toxicity.

摘要: Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions amphiphilic membranes modulation responses. find superwarfarins brodifacoum difenacoum increase lactate production cell death in neuroblastoma cells. In contrast, neither causes changes glioma cells have higher cholesterol content. After choleterol depletion, was viability reduced. Drug-membrane were examined by surface X-ray scattering using Langmuir monolayers dipalmitoylphosphatidylcholine and/or cholesterol. Specular reflectivity data revealed superwarfarins, but not warfarin, intercalate between molecules, whereas grazing incidence diffraction demonstrated lateral crystalline order the film. Neither agent showed significant containing >20% These findings demonstrate an affinity biomembranes suggest cellular responses these agents regulated