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

MARIANI, ME; SANCHEZ BORZONE, M; GARCIA, DA

CHEMISTRY AND PHYSICS OF LIPIDS

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 vol. 198 p. 39 - 45

0009-3084

The cyclic ketones, thujone and dihydrocarvone, are lipophiliccomponents of essential oils extracted from different plants, which haveproven insecticidal activity. The GABAA receptor is activated by theneurotransmitter GABA and is the action site of widely used neurotoxicpesticides. Many compounds that regulate GABAA receptor function interactwith membrane lipids, causing changes in their physical properties andconsequently, in the membrane dynamic characteristics that modulatereceptor macromolecules. In the present study, the biophysical effects ofthujone (a gabaergic reference compound) and dihydrocarvone (structurallyvery similar) were explored by using monomolecular films of DPPC as amodel membrane system, to gain insight into membrane-drug interaction.The compression isotherms showed that both ketones expand the DPPCisotherms and increase membrane elasticity. They penetrate the monolayerbut their permanence depends on the possibility of establishing molecularinteractions with the film component, favored by defects present in themembrane at the phase transition. Finally, by using Brewster anglemicroscopy (BAM) as a complementary technique for direct visualization ofthe study films, we found that incorporating ketone seems to reducemolecular repulsion among phospholipid headgroups. Our results reinforcethe notion that changes in membrane mechanics may be occurring in thepresence of the assayed ketones, suggesting that their interaction withthe receptor´s surrounding membrane may modulate or affect itsfunctionality, possibly as part of the mechanism of the bioactivitydescribed for thujone and DHC.