Synergy between verapamil and other multidrug -resistance modulators in model membranes.

Various cationic lipophilic compounds can reverse the multidrug resistance of cancer cells. Possible interaction between these compounds, which are known as modulators, has been assessed by measuring leakage of Sulphan blue from anionic liposomes, induced both by verapamil alone and by verapamil in combination with diltiazem, quinine, thioridazine or clomipramine. An equation was derived to quantify the permeation doses and Hill coefficients of the drugs and mixtures between them by simultaneous fitting of the experimental data.

Multidrug resistance modulator interactions with neutral and anionic liposomes: membrane binding affinity and membrane perturbing activity.

A variety of cationic lipophilic compounds (modulators) have been found to reverse the multidrug resistance of cancer cells. In order to determine the membrane perturbing efficacy and the binding affinity of such drugs in neutral and anionic liposomes, the leakage of Sulfan blue induced by five modulators bearing different electric charges was quantified using liposomes with and without phosphatidic acid (xEPA=0 and 0.1), at four lipid concentrations.

Effects of a series of dihydroanthracene derivatives on drug efflux in multidrug resistant cancer cells.

A set of 9,10-dihydro-9,10-ethano and ethenoanthracene derivatives was tested with the aim to quantify the effect observed on drug efflux. Structure activity relationships and molecular modeling studies allowed to define topological display of pharmacophoric groups for these reversal agents.

Effects of cholesterol on dye leakage induced by multidrug-resistance modulators from anionic liposomes.

Multidrug-resistance (MDR) in cancer cells is often associated with marked changes in the membrane cholesterol levels. To assess the cholesterol-dependence of MDR modulator efficiency in terms of the drug-membrane interactions, the ability of 5 MDR-modulators to induce the leakage of Sulphan blue through anionic liposomes was quantified at various mole fractions x(chol) of cholesterol (0-0.42).