Emerging screening platform characterises aminoquinoline structure-activity relationships with phospholipid layers.

• Tác giả: Bethany Crow, Roland Grafstrom, Vesa Hongisto, Mitali Kamat, Nikil Kapur, Ross Kelly, Andrew Nelson, Josh Owen, Ashi Rashid, William Stokes, Nicola William, Jeanine Williams
• Ngôn ngữ: eng
• Thông tin xuất bản: Netherlands : Bioelectrochemistry (Amsterdam, Netherlands) , 2025
• Bộ sưu tập: NCBI
• ID: 731452

Tóm tắt

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 pK