title: Membrane permeabilizing action of amphidinol 3 and theonellamide A in raft-forming lipid mixtures.
abstract: Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the dinoflagellate Amphidinium klebsii and the sponge Theonella spp., respectively. Both of these metabolites have been demonstrated to interact with membrane lipids ultimately resulting in a compromised bilayer integrity. In this report, the activity of AM3 and TNM-A in ternary lipid mixtures composed of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC):brain sphingomyelin:cholesterol at a mole ratio of 1:1:1 or 3:1:1 exhibiting lipid rafts coexistence is presented. It was found that AM3 has a more extensive membrane permeabilizing activity compared with TNM-A in these membrane mimics, which was almost complete at 15 μM. The extent of their activity nevertheless is similar to the previously reported binary system of POPC and cholesterol, suggesting that phase separation has neither beneficial nor detrimental effects in their ability to disrupt the lipid bilayer.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Espiritu
mesh_terms: D000475:Alkenes / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002784:Cholesterol; D004141:Dinoflagellida / Q000737:chemistry; D005452:Fluoresceins / Q000032:analysis; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D021962:Membrane Microdomains / Q000187:drug effects*; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D010713:Phosphatidylcholines; D011714:Pyrans / Q000302:isolation & purification / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013109:Sphingomyelins; D000095722:Amphidinols
chemical_list: D000475:Alkenes; D000935:Antifungal Agents; D002784:Cholesterol; D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D010456:Peptides, Cyclic; D010713:Phosphatidylcholines; D011714:Pyrans; D013109:Sphingomyelins; C438973:amphidinol 3; D000095722:Amphidinols; C581283:theonellamide A; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C007740:fluorexon