Skip to main content

Research Repository

Advanced Search

Lytic reactions of drugs with lipid membranes

Britt, Hannah M.; García-Herrero, Clara A.; Denny, Paul W.; Mosely, Jackie A.; Sanderson, John M.

Lytic reactions of drugs with lipid membranes Thumbnail


Authors

Hannah M. Britt

Clara A. García-Herrero

Jackie A. Mosely



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.

Citation

Britt, H. M., García-Herrero, C. A., Denny, P. W., Mosely, J. A., & Sanderson, J. M. (2019). Lytic reactions of drugs with lipid membranes. Chemical Science, 10(3), 674-680. https://doi.org/10.1039/c8sc04831b

Journal Article Type Article
Acceptance Date Nov 29, 2018
Online Publication Date Dec 3, 2018
Publication Date Jan 21, 2019
Deposit Date Dec 3, 2018
Publicly Available Date Mar 29, 2024
Journal Chemical Science
Print ISSN 2041-6520
Electronic ISSN 2041-6539
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 10
Issue 3
Pages 674-680
DOI https://doi.org/10.1039/c8sc04831b

Files

Published Journal Article (Advance online version) (1.4 Mb)
PDF

Copyright Statement
Advance online version This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.






You might also like



Downloadable Citations