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Evaluation of the Structure–Activity Relationship of Rifabutin and Analogs: A Drug–Membrane Study

Authors

  • Marina Pinheiro,

    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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  • Catarina Pereira-Leite,

    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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  • Mariana Arêde,

    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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  • Dr. Cláudia Nunes,

    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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  • João M. Caio,

    1. Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa (Portugal)
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  • Dr. Cristina Moiteiro,

    1. Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa (Portugal)
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  • Dr. Juan J. Giner-Casares ,

    1. Departamento de Química Física y Termodinámica, Universidad de Córdoba, España (Spain)
    2. Department of Interfaces, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14476 Potsdam (Germany)
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  • Dr. Marlene Lúcio,

    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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  • Dr. Gerald Brezesinski,

    1. Department of Interfaces, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14476 Potsdam (Germany)
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  • Dr. Luis Camacho,

    1. Departamento de Química Física y Termodinámica, Universidad de Córdoba, España (Spain)
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  • Dr. Salette Reis

    Corresponding author
    1. REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
    • REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto (Portugal)
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Abstract

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.

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