The ability of cationic amphiphilic compounds to depress the transition temperature of dipalmitoylphosphatidic acid liposomes depends on the spatial arrangement of the lipophilic moiety.
The hypothesis was tested with the help of model compounds that the ability of cationic amphiphilic drugs to depress the phase-transition temperature Tt of dipalmitoylphosphatidic acid (DPPA) liposomes depends on the spatial arrangement of the lipophilic moiety. The main structure of the compounds with identical cationic side chain was 1-dimethylamino-3-phenylpropane (compound I). A further phenyl ring was introduced either at C3 of the propane chain (compound II) to broaden the lipophilic moiety, or in para-position of the phenyl ring (compound III) to elongate it. As shown by differential scanning calorimetry, the reduction of Tt (control 64 degrees) amounted for compound I to 29 degrees, for compound II to 28 degrees and for compound III to 53 degrees. In order to assess the binding affinity of the compounds to DPPA, their inhibitory effect on 45Ca(2+)-binding to DPPA films was measured. The IC50 values were 2100 microM for compound I, 40 microM for compound II, and 9 microM for compound III. Thus, binding affinity corresponded with the hydrophobicity of the compounds. In contrast, the depressing effect on the transition temperature was only augmented by the additional phenyl ring when substituted in the elongating position.
Borchardt
K
K
Department of Pharmacology, University of Kiel, Federal Republic of Germany.
Heber
D
D
Klingmüller
M
M
Mohr
K
K
Müller
B
B
D002118:Calcium / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008081:Liposomes / Q000737:chemistry*; D008968:Molecular Conformation; D010712:Phosphatidic Acids / Q000737:chemistry*; D011437:Propylamines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature
D008081:Liposomes; D010712:Phosphatidic Acids; D011437:Propylamines; C072314:1-dimethylamino-3-phenylpropane; C031599:dipalmitoylphosphatidic acid; D002118:Calcium