A Semisynthetic 5-n-Alkylresorcinol Derivative and its Effect upon Biomembrane Properties

Abstract

MSAR (1-sulfate-3-myristoyl-5-pentadecylbenzene) is a semisynthetic derivative of 5-npentadecylresorcinol (C15:0). MSAR exhibits hemolytic activity against sheep erythrocytes with a EH 50 value of (35 ð 1.7) μm. At low concentrations MSAR also exhibits the ability to protect cells against their hypoosmotic lysis. This protective effect is significant as, at 0.1 μm of MSAR, the extent of osmotically induced cell lysis is reduced by approx. 20%. It was demonstrated that the 9-anthroyloxystearic acid signal was most intensively quenched by MSAR molecules, suggesting a relatively deep location of these molecules within the lipid bilayer. MSAR causes an increase of the fluorescence of the membrane potential sensitive probe. This indicates an alteration of the surface charge and a decrease of the local pH value at the membrane surface. At low bilayer content (1Ð4 mol%) this compound causes a significant increase of the phospholipid bilayer fluidity (both under and above the main phase transition temperature) of dipalmitoylphosphatidylcholine (DPPC) liposomes. At this low content MSAR slightly decreases the main phase transition temperature (T c ) value. The effects induced in the phospholipid bilayer by higher contents of MSAR molecules (5Ð10 mol%) make it impossible to determine the T c value and to evaluate changes of the membrane fluidity by using pyrene-labeled lipid. MSAR also causes a decrease of the activity of membrane-bound enzymes Ð red blood cell acetylcholinesterase (AChE) and phospholipase A 2 (PLA 2 ). MSAR decreases the AChE activity by 40% at 100 μm. The presence of MSAR in the liposomal membrane induces a complete abolishment of the lag time of the PLA 2 activity, indicating that these molecules induce the formation of packing defects in the bilayer which may result from imperfect mixing of phospholipids.

Biological activity of phenolic lipids

“…Resorcinolic lipids from rye bran and cardol from CNSL affected the properties of the hydrophobic region of the bilayer, but the properties of the subsurface part of the phospholipid bilayer were altered by anacardic acid, methylocardol, alkylphenol [21], and merulinic acid [41]. It was also found that 1-sulfate-3-myristoyl-5-pentadecylbenzene, a semisynthetic derivative of 5-npentadecylresorcinol, intensively quenched the 9-anthroyloxystearic acid signal, which suggests a relatively deep location of these molecules within the lipid bilayer [23]. Similar properties were also shown for cardanol (Stasiuk, unpublished data).…”

“…It was demonstrated that 1-sulfate-3-myristoyl-5-pentadecylbenzene (pentadecylresorcinol derivative) is a more hydrophilic compound, with a CMC value of 0.893 lM [23]. A micellization study of 2,4-sodium dissulfonate-5-npentadecylphenol synthesized from hydrogenated cardanol showed that the CMC depends on temperature and electrolyte (potassium chloride) concentration in the subhase buffer and that it decreased with increasing electrolyte concentration and temperature.…”

“…This depended on the chemical structure of tested phenolic lipid molecules. 1-sulfate-3-myristoyl-5-pentadecylbenzene present in the lecithin liposomal bilayers caused a drastic decrease in the first phase of the cobra venom phospholipase A2 kinetic curve (called the ''lag time''), which suggests that this compound can cause defects in phospholipid packing within the bilayer [23]. A strong inhibitory activity was observed for cobra venom, phospholipase A2, in the presence of a mixture of bacterial alkylresorcinols in lecithin black lipid membrane and phospholipid emulsion systems.…”

Alquilresorcinoles: Compuestos Naturales con Importancia Biológica

“…Como se mencionó anteriormente, los AR poseen una gran afinidad con bicapas lípidicas (i.e., membranas celulares), interactuando con fosfolípi-dos mediante puentes de hidrógeno (Stasiuk et al, 2007) aumentando la permeabilidad de la membrana cuando ésta se encuentra en un medio acuoso rico en 5-n-alquilresorcinoles. Cuando estos compuestos son incorporados en la bicapa durante su formación, los liposomas resultantes son más eficaces encapsulando y preservando solutos solubles en agua, que cuando no se encuentran AR en el medio (Gubernator et al, 1999; Stasiuk y Kozubek, 2010).…”