Calorimetric, 13C NMR, and 31P NMR studies on the interaction of some phenothiazine derivatives with dipalmitoyl phosphatidylcholine model membranes

Modulation of membrane structure by Ca2+ and dibucaine as detected by 31P NMR

“…2 (b) which requires further attention is the large negative value of the effective chemical shift anisotropy [ 1] EFF = (A o CSA --53 ppm) observed. Such effects suggest an ability of the local anaesthetic to induce appreciably more order in the phosphate region, which is consistent with recent observations for phosphatidylcholine-local anaesthetic dispersions [16]. A final technical point concerns the need for a freeze-thaw procedure in order to observe these spectral changes.…”

The Role of the Membrane Actions of Phenothiazines and Flavonoids as Functional Modulators

“…Cater et al [57] found that CPZ (9) caused a melting temperature decrease and transition peak broadening in DPPC membranes. Virtually the same results were obtained later on by Frenzel et al [58] in DPPC mixtures with CPZ (9) and diethazine (7). It was, however, noticed that at high CPZ (9) concentrations (above 15 mol %) the calorimetric peaks became narrow again.…”

“…The observation was attributed by the authors to the formation of an interdigitated phase. The possibility of the existence of such a phase at high CPZ (9) concentrations was also suggested by Frenzel et al [58] as they observed that the calorimetric peaks, broadened at low CPZ (9) concentrations, became narrow again at high concentrations of the drug. Besides CPZ (9), TFP (5) is another phenothiazine derivative whose interaction with membranes is relatively well known.…”

“…The IC 50 value obtained in our study for silybin (52) was similar to that recorded by Trompier et al [224] for inhibition of LTC4 transport by this flavanolignan. Two of the four synthetic genistein derivatives studied, IFG10 (57) and IFG12 (58), and natural flavonoids apigenin (23), sophoraisoflavone A (60), and genistein (42), were also shown to be MRP1 inhibitors; their IC 50 values were significantly higher than those for the most active compounds [233]. Isoflavone prunetin (44) was not active, while synthetic isoflavones IFG8 (56) and IFG18 (59) were only slightly effective; however, their IC 50 values were not achieved within all ranges of concentration studied.…”

“…CPZ (9) was found to stabilize the bilayer arrangement of egg PE, the lipid that relatively easily adopted the inverted hexagonal packing mode [61]. In DPPC multilayers the presence of CPZ (9) or diethazine (7) resulted in enhanced mobility in the acyl chain region of the model membrane and a mobility reduction of the polar DPPC headgroups [58]. The authors proposed that phenothiazine derivatives are incorporated into membranes in such a way that the ring system is placed not far beyond the lipid's glycerol backbone and the cationic side chain is located near the polar headgroups.…”