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Evaluation of the Structure–Activity Relationship of Rifabutin and Analogs: A Drug–Membrane Study
Author(s) -
Pinheiro Marina,
PereiraLeite Catarina,
Arêde Mariana,
Nunes Cláudia,
Caio João M.,
Moiteiro Cristina,
GinerCasares Juan J.,
Lúcio Marlene,
Brezesinski Gerald,
Camacho Luis,
Reis Salette
Publication year - 2013
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201300262
Subject(s) - rifabutin , membrane , chemistry , antimycobacterial , membrane fluidity , phosphatidylcholine , biological membrane , small angle x ray scattering , biophysics , brewster's angle , vesicle , scattering , biochemistry , phospholipid , optics , clarithromycin , mycobacterium tuberculosis , medicine , tuberculosis , physics , pathology , biology , antibiotics , brewster
This work focuses on the influence of rifabutin and two novel analogs, namely, N′ ‐acetyl‐rifabutin and N ′‐butanoyl‐rifabutin, on the biophysical properties of lipid membranes. Monolayers and multilamellar vesicles composed of egg L ‐α‐phosphatidylcholine:cholesterol in a molar ratio of 4:1 are chosen to mimic biological membranes. Several accurate biophysical techniques are used to establish a putative relationship between the chemical structure of the antimycobacterial compounds and their activity on the membranes. A combination of in situ experimental techniques, such as Langmuir isotherms, Brewster angle microscopy, polarization‐modulated infrared reflection–absorption spectroscopy, and small‐angle X‐ray scattering, is used to assess the drug–membrane interaction. A relationship between the effect of a drug on the organization of the membranes and their chemical structure is found and may be useful in the development of new drugs with higher efficacy and fewer toxic effects.