title: Molecular interaction of Rifabutin on model lung surfactant monolayers.
abstract: Tuberculosis is one of the most relevant problems for global health care. The design of new drugs against tuberculosis is aimed at maximizing impact against the disease, as well as minimizing the toxicological effect on the lung surfactant. In this work, the antituberculosis drug Rifabutin is studied in combination with phospholipid Langmuir monolayers as models of the lung surfactant monolayer. The zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the anionic 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) were used as model phospholipids. A combination of in situ experimental techniques of Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and UV-vis reflection spectroscopy with computer simulations has been used. The interactions between Rifabutin and the DPPC and DPPG Langmuir monolayers were described as the formation of an inclusion complex. The phospholipid-Rifabutin inclusion complex prevents the penetration of the Rifabutin into the alkyl chain region of the phospholipids, leading to a disruption of the monolayer structure and a possible toxicological effect.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
authors.forename: João M
authors.initials: JM
authors.lastname: Caio
authors.forename: Cristina
authors.initials: C
authors.lastname: Moiteiro
authors.forename: María T
authors.initials: MT
authors.lastname: Martín-Romero
authors.forename: Luis
authors.initials: L
authors.lastname: Camacho
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Giner-Casares
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010743:Phospholipids / Q000737:chemistry*; D011312:Pressure; D011663:Pulmonary Surfactants / Q000737:chemistry*; D017828:Rifabutin / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000995:Antitubercular Agents; D010743:Phospholipids; D011663:Pulmonary Surfactants; D017828:Rifabutin