A scanning calorimetric study of the interaction of anthracyclines with neutral and acidic phospholipids alone and in binary mixtures.
High sensitivity differential scanning calorimetry was employed to study the thermotropic behavior of multilamellar vesicles of neutral and acidic phospholipids and binary mixtures thereof in the presence of anthracycline antibiotics. Adriamycin and its lipophilic analogue, N-trifluoroacetyladriamycin-14-valerate (AD32) were investigated and compared to chlorpromazine and quinidine with respect to their ability to affect the pretransition and the main transition of the phospholipids suspended in physiological buffer. With liposomes of neutral dipalmitoylphosphatidylcholine the observed effects paralleled to some extent the corresponding octanol/buffer partition coefficients, with adriamycin being the least effective. Calorimetric measurements on liposomes prepared from pure dipalmitoylphosphatidylglycerol or from binary mixtures of dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine showed that modulation of bilayer properties by adriamycin was greatly enhanced in the presence of negatively charged lipid headgroups presumably as a result of electrostatic interactions. AD32 interacted differently from adriamycin with the acidic bilayers at low drug concentrations, in a manner similar to that of its interaction with neutral bilayers. At high drug concentrations both adriamycin and AD32 produced transitions with multiple peaks not exhibited by chlorpromazine and quinidine which may be the result of a specific association of the anthracyclines with dipalmitoylphosphatidylglycerol. All four drugs produced only minor changes in the enthalpy of the main transition of the investigated lipids. The present findings are discussed in terms of their possible physiological relevance.
Constantinides
P P
PP
Inouchi
N
N
Tritton
T R
TR
Sartorelli
A C
AC
Sturtevant
J M
JM
D000903:Antibiotics, Antineoplastic; D002152:Calorimetry, Differential Scanning; D002746:Chlorpromazine / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers; D008081:Liposomes; D009279:Naphthacenes / Q000494:pharmacology; D009994:Osmolar Concentration; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011802:Quinidine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D008051:Lipid Bilayers; D008081:Liposomes; D009279:Naphthacenes; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011663:Pulmonary Surfactants; C016163:valrubicin; D004317:Doxorubicin; D011802:Quinidine; D002746:Chlorpromazine; C030345:1,2-dipalmitoylphosphatidylglycerol