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The Influence of Rifabutin on Human and Bacterial Membrane Models: Implications for Its Mechanism of Action

The Influence of Rifabutin on Human and Bacterial Membrane Models: Implications for Its Mechanism of Action

Marina Pinheiro, Cláudia Nunes, João M Caio, Cristina Moiteiro, Marlene Lúcio, Gerald Brezesinski, Salette Reis

J Phys Chem B. 2013 May 23;117(20):6187-93.

PMID: 23617457

Abstract:

This work focuses on the interaction of the antibiotic Rifabutin (RFB) with phospholipid membrane models using small- and wide-angle X-ray scattering (SAXS and WAXS) to assess drug-membrane interactions. The effect of different concentrations of RFB on human and bacterial cell membrane models was studied using multilamellar vesicles (MLVs) at the physiological pH (7.4). In this context, MLVs of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) were chosen to mimic the human cell membrane. To mimic the bacterial cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were used. The results support a perturbation of the lipid bilayers caused by RFB, especially in the bacterial membrane model, inducing phase separation that might compromise the integrity of the bacterial membrane. Therefore, the different effects of this antibiotic depending on the concentration, the charge of the phospholipid headgroup, and the membrane organization may be related with the RFB antibiotic activity and the side effects, and should be accounted for during the anti-tuberculosis (anti-TB) drug design.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP18656387	1,2-Dimyristoyl-rac-glycero-3-phosphocholine		18656-38-7	Price

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