| Autor: |
Efimova SS; Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia., Martynyuk VA; Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia., Zakharova AA; Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia., Yudintceva NM; Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia., Chernov NM; Saint-Petersburg State Chemical Pharmaceutical University, Professor Popov 14, 197022 Saint Petersburg, Russia., Yakovlev IP; Saint-Petersburg State Chemical Pharmaceutical University, Professor Popov 14, 197022 Saint Petersburg, Russia., Ostroumova OS; Institute of Cytology of Russian Academy of Sciences, Tikhoretsky 4, 194064 Saint Petersburg, Russia. |
| Abstrakt: |
Herein, we report that chromone-containing allylmorpholines can affect ion channels formed by pore-forming antibiotics in model lipid membranes, which correlates with their ability to influence membrane boundary potential and lipid-packing stress. At 100 µg/mL, allylmorpholines 1 , 6 , 7 , and 8 decrease the boundary potential of the bilayers composed of palmitoyloleoylphosphocholine (POPC) by about 100 mV. At the same time, the compounds do not affect the zeta-potential of POPC liposomes, but reduce the membrane dipole potential by 80-120 mV. The allylmorpholine-induced drop in the dipole potential produce 10-30% enhancement in the conductance of gramicidin A channels. Chromone-containing allylmorpholines also affect the thermotropic behavior of dipalmytoylphosphocholine (DPPC), abolishing the pretransition, lowering melting cooperativity, and turning the main phase transition peak into a multicomponent profile. Compounds 4 , 6 , 7 , and 8 are able to decrease DPPC's melting temperature by about 0.5-1.9 °C. Moreover, derivative 7 is shown to increase the temperature of transition of palmitoyloleoylphosphoethanolamine from lamellar to inverted hexagonal phase. The effects on lipid-phase transitions are attributed to the changes in the spontaneous curvature stress. Alterations in lipid packing induced by allylmorpholines are believed to potentiate the pore-forming ability of amphotericin B and gramicidin A by several times. |
