Conformational analysis of suloctidil and derivatives inserted in lipid layers

Interaction between suloctidil (CP 556 S) and lipids (phosphatidylcholine, phosphatidylserine) is studied using a new conformational analysis procedure. This analysis is extended to two compounds related to suloctidil but bearing no protonable group (CP 894 S) or of different hydrophobicity (CP 1136 S). It gives a molecular description of the mode of insertion of the drugs into the lipid layer. The influence of the calculated lipid-drug interaction and area occupied per drug molecule in the lipid layer is tentatively related to the effect on the lipid dynamics. For a given conformer, an effect on the lipid dynamics is expected only if (a) the area occupied per conformer is similar to that of the lipid and/or (b) the drug-lipid interaction energy is equal or superior to that of the lipid-lipid interaction. These predictions are analyzed in terms of the available experimental data.