Ellipticine derivatives interacting with model membranes. Influence of quaternarization of nitrogen-2.
Four compounds of the ellipticine family were examined in their interaction with liposomes and with an isolated bacterial membrane. The physicochemical methods used detected only minor differences between the properties of the amphiphilic drugs (ellipticine and 2-methyl-ellipticinium) and the two dipolar drugs (9-hydroxy-ellipticine and 2-methyl 9-hydroxy-ellipticinium). The amphiphilic drugs were able to become associated to anionic liposomes in a 20-30% excess of charge neutralization, and seem to penetrate deeper into the lipid layer than the two dipolar drugs. It was also shown that ellipticine penetrates deeper into liposomes membrane than into natural membrane used. In contrast with what can be postulated from the literature dealing with the behaviour of quaternarized drugs, it seems that ellipticine and its quaternarized analogues present fast diffusion through multilayered vesicles. On the whole, the membrane effects of the ellipticines studied here are not different for quaternarized drugs and for drugs not permanently charged, but are influenced by the existence on the molecules of a second polar function.
D000470:Alkaloids / Q000494:pharmacology*; D002412:Cations; D002462:Cell Membrane / Q000187:drug effects*; D004058:Diffusion; D004611:Ellipticines / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes; D010715:Phosphatidylglycerols; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002412:Cations; D004611:Ellipticines; D008081:Liposomes; D010715:Phosphatidylglycerols; C027767:elliptinium; C027211:2-methylellipticinium; C008009:9-hydroxyellipticine