Crow, B., Grafstrom, R., Hongisto, V. et al. (9 more authors) (2025) Emerging screening platform characterises aminoquinoline structure–activity relationships with phospholipid layers. Bioelectrochemistry, 164. 108927. ISSN 1567-5394
Abstract
Aminoquinolines (AQ) and substituted aminoquinolines (s-AQ) interact with electrochemically monitored supported dioleoyl phosphatidylcholine (DOPC) monolayers and immobilised artificial membranes (IAM) on HPLC column. The electrochemical sensor records adsorption/partition of the compound on and into the layer as well as specific interactions due to the location of the compound in the layer. HPLC-IAM technology measures the partition coefficient between the solution and phospholipid including partition due to interaction of the positive molecular charge with the phospholipid polar heads. The monolayer interaction results were combined and normalised for the neutral compounds’ lipophilicity as a log biomembrane affinity index (‘log BAI’) to exemplify charge and structural features in the interaction. A ChimeraX molecular modelling procedure was used to aid in the results interpretation. A compound ToxScore value was derived from 5 in vitro assays. The ‘log BAI’ exhibited a linear relationship with the AQ pKa values showing that the interaction was related to the molecular positive charge and to the electron donating properties of the –NH₂ group. The correlation outliers showed a tendency/no tendency to H-bonding with the polar groups and a superficial/deeper location respectively in the phospholipid layer. The s-AQ ‘log BAI’ value displayed a power correlation with the compounds’ ToxScore values.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mechanical Engineering (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Mar 2025 09:53 |
Last Modified: | 05 Mar 2025 09:53 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bioelechem.2025.108927 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224022 |