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• W2038546265 abstract "Abstract This study was designed to test the hypothesis that lipophilic cationic drugs with only roughly similar structures mediate the reversal of multidrug-resistance (MDR) by interacting with membrane phospholipids. The permeation properties of MDR-modulators and non-modulators were studied by quantifying their ability to induce the leakage of Sulphan blue through the membrane of negatively charged unilamellar liposomes. Of the 22 compounds under investigation, only those bearing a net positive electric charge per molecule (z) ≥0.2 induced dye leakage. All these efficient drugs are well-known MDR-modulators: calcium-channel blockers (propranolol, verapamil, diltiazem and dipyridamole), calmodulin antagonists (clomipramine and thioridazine) and antiparasitic agents (mepacrine, thioacridine derivatives and quinine). The non-modulators tested, including antineoplasic agents and steroids, did not induce any membrane permeation. The permeation process was a co-operative one (1.1 &lt; Hill coefficient &lt; 4.1) and the permeation doses inducing 50% dye leakage (PD50) were 1.9–11.2 mm. The permeation ability of the MDR-modulators (log(1/PD50)) increased significantly with octanol-buffer distributions per unit net electric charge ((logD)/z). The results provide evidence that a complex interplay occurs between the electric charge and the lipophilicity of the MDR-modulators when a dye leakage is induced through model membranes, and probably also when the MDR is reversed in leukaemic cells." @default.
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• W2038546265 date "2000-03-01" @default.
• W2038546265 modified "2023-09-27" @default.
• W2038546265 title "Membrane Permeation by Multidrug-resistance-modulators and Non-modulators: Effects of Hydrophobicity and Electric Charge" @default.
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• W2038546265 doi "https://doi.org/10.1211/0022357001773977" @default.
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