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.
Keywords: antibiotics; monolayers; phospholipids; structure-activity relationships; vesicles.
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