Surface activity of thymol: implications for an eventual pharmacological activitty

SÁNCHEZ M. E., TURINA A., GARCIA D., NOLAN V. AND PERILLO M. A.

COLLOIDS AND SURFACES

Elsevier

Año: 2004 vol. 34 p. 77 - 86

0166-6622

In the present work, we studied the ability of thymol to affect the organization of model membranes and the activity of an intrinsic membrane protein, the GABA receptor. In this paper, we tried to elucidate if the action mechanism of the terpen at molecular level, involves its binding to the receptor protein, changes in the organization of the receptor molecular environment, or both. The self-aggregation of thymol in water with a critical micellar concentration (CMC) = 4mMand its ability to penetrate in monomolecular layers of soybean phosphatidilcholine (sPC) at the air-water interface, even at surface pressures above the equilibrium, lateral pressure of natural bilayers were demonstrated. Thymol affected the self-aggregation of Triton X-100 and the topology of sPC vesicles. It also increased the polaritry of the membrane environment sensed by the electrochromic dye merocyanine. A dipolar moment of 1.341 Debye was calculated from its energy minimized structure. Its effect on the binding of [3H]-flunitrazepam ([3H]-FNZ) to chick brain synaptosomal membranes changed qualitatively from a tendency to the inhibition to a clear activatory regime, up on changing the phase state of the terpen (from a monomeric to a self-aggregated state). Above its CMC, thymol increased the affinity of the bindiing of [3H-FNZ] without changing the receptor density. The activatory effect of thymol on the bimding of [3H-FNZ] was observed even in the presence of allosteric activator gamma-aminobutyric acid (GABA) at a concentration of maximal activity, and was blocked by the GABA antagonist bicuculine. Changes in thevdipolar arrangement and in the molecular packing of GABA-R environment are discussed as possible mediators of the action mechanism of thymol.