Effects of bioactive monoterpenic ketones on membrane organization. A langmuir film study

The cyclic ketones, thujone and dihydrocarvone, are lipophilic components of essential oils extracted from different plants, which have proven insecticidal activity. The GABA(A) receptor is activated by the neurotransmitter GABA and is the action site of widely used neurotoxic pesticides. Many compounds that regulate GABAA receptor function interact with membrane lipids, causing changes in their physical properties and consequently, in the membrane dynamic characteristics that modulate receptor macromolecules. In the present study, the biophysical effects of thujone (a gabaergic reference compound) and dihydrocarvone (structurally very similar) were explored by using monomolecular films of DPPC as a model membrane system, to gain insight into membrane-drug interaction. The compression isotherms showed that both ketones expand the DPPC isotherms and increase membrane elasticity. They penetrate the monolayer but their permanence depends on the possibility of establishing molecular interactions with the film component, favored by defects present in the membrane at the phase transition. Finally, by using Brewster angle microscopy (BAM) as a complementary technique for direct visualization of the study films, we found that incorporating ketone seems to reduce molecular repulsion among phospholipid headgroups. Our results reinforce the notion that changes in membrane mechanics may be occurring in the presence of the assayed ketones, suggesting that their interaction with the receptor's surrounding membrane may modulate or affect its functionality, possibly as part of the mechanism of the bioactivity described for thujone and DHC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.