Interaction of Selected Phenylpropenes with Dipalmitoylphosphatidylcholine Membrane and Their Relevance to Antibacterial Activity.

ABSTRACT

The effect of structurally closely related phenylpropenes (PPs), estragole, anethole, eugenol, and isoeugenol, on the fluidity of dipalmitoyl phosphatidyl choline (DPPC) liposome membrane was investigated by DSC, Raman, and fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared by thin-film hydration method at various DPPCPP molar ratios. The DPH anisotropy measurements of blank and PP-loaded liposomes were performed at 28, 41, and 50 °C, which correspond, respectively, to gel phase, main transition temperature of DPPC, and liquid phase. The Raman images showed the formation of nano- and micrometric spherical multi-lamellar vesicles. All studied PPs exhibited a membrane fluidizing effect which was reinforced by the presence of phenolic hydroxyl group in eugenol and isoeugenol. The PPs interacted with the choline head group and the alkyl chains of DPPC membrane, wherein isoeugenol and anethole possessing the same C7-C8 position of the double bond in the propenyl side chain, incorporated deeply in the bilayer. Additionally, the PPs were analyzed for antibacterial activity against E. coli by macrobroth dilution method. Anethole and estragole were more efficient in inhibiting the bacterial growth than eugenol and isoeugenol. We conclude that the fluidizing effect of PPs on the membrane is a common mechanism that is not related to the hydrophobicity of the PP molecule. Besides, other target sites may be involved in PP antibacterial activity against Gram-negative bacteria. The greater hydrophobicity of these PPs may contribute to their penetrability through the outer bacterial membrane.