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Issue 3, 2019

Lytic reactions of drugs with lipid membranes

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Abstract

Propranolol is shown to undergo lipidation reactions in three types of lipid membrane: (1) synthetic single-component glycerophospholipid liposomes; (2) liposomes formed from complex lipid mixtures extracted from E. coli or liver cells; and (3) in cellulo in Hep G2 cells. Fourteen different lipidated propranolol homologues were identified in extracts from Hep G2 cells cultured in a medium supplemented with propranolol. This isolation of lipidated drug molecules from liver cells demonstrates a new drug reactivity in living systems. Acyl transfer from lipids to the alcoholic group of propranolol was favoured over transfer to the secondary amine. Migration of acyl groups from the alcohol to the amine was diminished. Other drugs that were examined did not form detectable levels of lipidation products, but many of these drugs did affect the lysolipid levels in model membranes. The propensity for a compound to induce lysolipid formation in a model system was found to be a predictor for phospholipidosis activity in cellulo.

Graphical abstract: Lytic reactions of drugs with lipid membranes

Supplementary files

Article information


Submitted
29 Oct 2018
Accepted
29 Nov 2018
First published
03 Dec 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 674-680
Article type
Edge Article

Lytic reactions of drugs with lipid membranes

Hannah M. Britt, C. A. García-Herrero, P. W. Denny, J. A. Mosely and J. M. Sanderson, Chem. Sci., 2019, 10, 674 DOI: 10.1039/C8SC04831B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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