title: Differential interactions of rifabutin with human and bacterial membranes: implication for its therapeutic and toxic effects.
abstract: This work focuses on the interaction of rifabutin (RFB), a naphthalenic ansamycin, with membrane models. Since the therapeutic and toxic effects of this class of drugs are strongly influenced by their lipid affinity, we concerned specifically on the ability of this antibiotic to affect the membrane biophysical properties. The extent of the interaction between RFB and membrane phospholipids was quantified by the partition coefficient (K(p)), using membrane model systems that mimic the human (liposomes of 1,2-dimyristoyl-sn-glycero-phosphocholine, DMPC) and the bacterial (liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DMPG) plasma membranes. To predict the drug location in the membranes, fluorescence quenching and lifetime measurements were carried out using the above-mentioned membrane models labeled with fluorescent probes. Steady-state anisotropy measurements were also performed to evaluate the effect of RFB on the microviscosity of the membranes. Overall, the results support that RFB has higher affinity for the bacterial membrane mediated by electrostatic interactions with the phospholipid head groups.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, Porto 4050-313, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Mariana
authors.initials: M
authors.lastname: Arêde
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.forename: João M
authors.initials: JM
authors.lastname: Caio
authors.forename: Cristina
authors.initials: C
authors.lastname: Moiteiro
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers; D008081:Liposomes; D017828:Rifabutin / Q000494:pharmacology*; D014783:Viscosity
chemical_list: D000995:Antitubercular Agents; D008051:Lipid Bilayers; D008081:Liposomes; D017828:Rifabutin