(393b) Lipid Membrane Bilayer Destabilization By Amphiphilic Coumarin: A Biophysical Study for Cancer Applications

The interaction between the phospholipid cell membrane and the drug molecules can be quantified by various biophysical and biochemical methods. This study is important is understanding the pharmacology of novel molecules. Though the phospholipid membrane is not the final target of the drug molecule, a knowledge on this initial interaction is necessary to predict the efficacy of the drug. The penetration efficiency of a hydrophilic molecule can be enhanced by inducing amphiphilicity to it.

We have investigated the binding and membrane penetration ability of fluorescent amphiphilic amino coumarin molecules using model cell membranes or liposomes. Firstly, the binding of the molecules to the lipid bilayer was established by surface charge and fluorescence spectroscopy. Then the cell membrane perturbation by these molecules was analysed by examining the phase behaviour of the phospholipids. Based on this, we proposed a combination mechanism of carpet and flip-flop through which these molecules destabilize the membrane. The proposed mechanism is attributed to the induced amphiphilicity in the coumarin molecules and is dependent on concentration. These results conform to the preliminary biological in-vitro activity. These fluorescent amphiphilic molecules have their proposed application in cancer diagnosis and therapeutics.