Interactions of a fungistatic antibiotic, griseofulvin, with phospholipid monolayers used as models of biological membranes.
Griseofulvin (GF) is an oral antibiotic for widely occurring superficial mycosis in man and animals caused by dermaphyte fungi; it is also used in agriculture as a fungicide. The mechanism of the biological activity of GF is poorly understood. Here, the interactions of griseofulvin with lipid membranes were studied using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), and 1,2-myristoyl-sn-glycero-3-phosphoethanolamine (DMPE) monolayers spread at the air/water interface. Surface pressure (Pi), electric surface potential (Delta V), grazing incidence X-ray diffraction (GIXD), and Brewster angle microscopy (BAM) were used for studying pure phospholipid monolayers spread on GF aqueous solutions, as well as mixed phospholipid/GF monolayers spread on pure water subphase. Moreover, phospholipase A2 (PLA2) activity toward DLPC monolayers and molecular modeling of the GF surface and lipophilic properties were used to get more insight into the mechanisms of GF-membrane interactions. The results obtained show that GF has a meaningful impact on the film properties; we propose that nonpolar interactions are by and large responsible for GF retention in the monolayers. The modification of membrane properties can be detected using both physicochemical and enzymatic methods. The results obtained may be relevant for elaborating GF preparations with increased bioavailability.
Corvis
Yohann
Y
Groupe d'Etude des Vecteurs Supramoléculaires du Médicament UMR 7565 CNRS/Université Henri Poincaré Nancy 1, Faculté des Sciences, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France.
Barzyk
Wanda
W
Brezesinski
Gerald
G
Mrabet
Nadir
N
Badis
Mounia
M
Hecht
Sabrina
S
Rogalska
Ewa
E
D000388:Air; D000935:Antifungal Agents / Q000737:chemistry*; D002384:Catalysis; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004058:Diffusion; D006118:Griseofulvin / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions
D000935:Antifungal Agents; D010743:Phospholipids; D012996:Solutions; D006118:Griseofulvin; D010741:Phospholipases A; D054467:Phospholipases A2