The antimalarial agent halofantrine perturbs phosphatidylcholine and phosphatidylethanolamine bilayers: A differential scanning calorimetric study

The interaction of halofantrine with phosphatidylcholine and phosphatidylet hanolamine bilayers has been investigated by differential scanning calorime try. Halofantrine caused a broadening of the gel to liquid crystalline phas e transition endotherm of the phosphatidylcholines. A decrease in the trans ition temperature T-m and enthalpy (Delta H) of transition was also observe d. This varied with the chain length of the phospholipid and was more prono unced with short chain members. Halofantrine-induced changes to the thermot ropic characteristics of dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers suggested that the penetration of halofantrine into the bilayer wa s diminished in the presence of cholesterol. A more complex calorimetric pr ofile was observed in the interaction of halofantrine with phosphatidyletha nolamines and the results suggested that halofantrine did not disrupt the c ooperativity of the phosphatidylethanolamine bilayers to the same extent as that observed with the phosphatidylcholines. Halofantrine caused significa nt perturbation of phospholipids and this property might have an important bearing on its pharmacodynamic effects.