QSAR analysis of substituent effects on tambjamine anion transporters12. Issue 2 (8th December 2015)

• Record Type: Journal Article
• Authors: Knight, Nicola J.; Hernando, Elsa; Haynes, Cally J. E.; Busschaert, Nathalie; Clarke, Harriet J.; Takimoto, Koji; García-Valverde, María; Frey, Jeremy G.; Quesada, Roberto; Gale, Philip A.
• Is Part Of: Chemical science. Volume 7:Issue 2(2016:Feb.)
• Page Start: 1600
• Page End: 1608
• Publication Date: 2015-12-08
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc03932k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A QSAR analysis of the transmembrane anion transport activity of 43 synthetic tambjamine analogs allowed rationalization of this activity according to their lipophilicity and structural parameters. Abstract : The transmembrane anion transport activity of 43 synthetic molecules based on the structure of marine alkaloid tambjamine were assessed in model phospholipid (POPC) liposomes. The anionophoric activity of these molecules showed a parabolic dependence with lipophilicity, with an optimum range for transport efficiency. Using a quantitative structure–transport activity (QSAR) approach it was possible to rationalize these results and to quantify the contribution of lipophilicity to the transport activity of these derivatives. While the optimal value of log P and the curvature of the parabolic dependence is a property of the membrane (and so similar for the different series of substituents) we found that for relatively simple substituents in certain locations on the tambjamine core, hydrophobic interactions clearly dominate, but for others, more specific interactions are present that change the position of the membrane hydrophobicity parabolic envelope.