Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Pinheiro, M (Autor) Outra; Amenitsch, H (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: Membranes

Vol. 9

Página Final: 141

ISSN: 2077-0375

Editora: MDPI

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-00R-825

DOI: 10.3390/membranes9110141

Abstract (EN): This work focuses on the interaction of the novel and representative antituberculosis (anti-TB) drug bedaquiline (BDQ) with different membrane models of eukaryotic and prokaryotic cells. The effect of BDQ on eukaryotic cell membrane models was assessed using liposomes, namely, multilamellar vesicles (MLVs) made of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and also a mixture of DMPC and cholesterol (CHOL) (8:2 molar ratio). To mimic the prokaryotic cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and 1,1 ' 2,2 '-tetra-oleoyl-cardiolipin (TOCL) were chosen. Powerful biophysical techniques were employed, including small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), to understand the effect of BDQ on the nanostructure of the membrane models. The results showed that BDQ demonstrated a pronounced disordering effect in the bacterial cell membrane models, especially in the membrane model with cardiolipin (CL), while the human cell membrane model with large fractions of neutral phospholipids remained less affected. The membrane models and techniques provide detailed information about different aspects of the drug-membrane interaction, thus offering valuable information to better understand the effect of BDQ on their target membrane-associated enzyme as well as its side effects on the cardiovascular system.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10