Issue 2, 2016

QSAR analysis of substituent effects on tambjamine anion transporters

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.

Graphical abstract: QSAR analysis of substituent effects on tambjamine anion transporters

Supplementary files

Article information

Article type
Edge Article
Submitted
16 oct. 2015
Accepted
17 nov. 2015
First published
08 dic. 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 1600-1608

Author version available

QSAR analysis of substituent effects on tambjamine anion transporters

N. J. Knight, E. Hernando, C. J. E. Haynes, N. Busschaert, H. J. Clarke, K. Takimoto, M. García-Valverde, J. G. Frey, R. Quesada and P. A. Gale, Chem. Sci., 2016, 7, 1600 DOI: 10.1039/C5SC03932K

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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