title: Membrane activity of tetra-p-guanidinoethylcalix[4]arene as a possible reason for its antibacterial properties.
abstract: Tetra-p-guanidinoethylcalix[4]arene trifluoroacetate salt (CX1) was synthesized recently as an antibacterial agent. It showed to be active in vitro against various Gram-positive and Gram-negative bacteria. To get more insight in the mechanism of the biological activity of this derivative, it was studied upon interactions with model lipid membranes. Langmuir monolayers were formed with zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine or 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, and with anionic 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine. The two classes of lipids were used, respectively, as model lipids of the eukaryotic and bacterial cell membranes. The monolayers were exposed to CX1 at different concentrations around the minimum inhibitory concentration found for E. coli . The surface pressure-area and surface potential-area compression isotherms, as well as Brewster angle microscopy and polarization-modulation infrared reflection-absorption spectroscopy, were employed to study the monolayers. The results obtained show a higher affinity of CX1 for the anionic lipids, indicating importance of charge-charge interactions. On the basis of a comparative study of the behavior of CX1 and that of p-guanidinoethylphenol trifluoroacetate salt, we propose that interplay of charge-charge and apolar interactions between CX1 and lipids is responsible for the important reorganization of model membranes. This proposal may be helpful in developing new antibacterial calixarene derivatives.
authors.affiliation: Equipe GEVSM, Structure et Réactivité des Systèmes Moléculaires Complexes, UMR 7565 Nancy Université/CNRS, Vandoeuvre-lès-Nancy, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sautrey
authors.forename: Monika
authors.initials: M
authors.lastname: Orlof
authors.forename: Beata
authors.initials: B
authors.lastname: Korchowiec
authors.forename: Jean-Bernard Regnouf
authors.initials: JB
authors.lastname: de Vains
authors.forename: Ewa
authors.initials: E
authors.lastname: Rogalska
mesh_terms: D000042:Absorption; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D010743:Phospholipids / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D006146:Guanidines; D010743:Phospholipids; C512158:tetra-para-guanidinoethyl-calix(4)arene