Interaction of Drugs and Medicinal Plant Extracts with Membranes

Several natural plant extracts and pharmacological drugs are biologically active as antidepressant,
antimicrobial, anticancer and anti-inflammatory agents. The diverse healing properties of these compounds
and the equivalent efficacy of their optical isomers suggest that their activity might be exerted via
modulation of membrane properties and of transmembrane proteins residing therein. The interactions of
these small molecules with lipid bilayers and membrane proteins are examined using MD simulations.
The goal is to (1) drive the design of affordable new anticancer and antimicrobial agents to counter the problem
of multidrug resistance in pathogens and cancer cells (2) Obtain insights into the mechanism of action of natural plant extracts of medicinal value, which are being used in Eastern medicine for millenia.

Examples of such molecules include the Indian spice extract: curcumin, which gives Indian food its
characteristic yellow color; and cyclic terpenes: compounds present in citrus fruits and the leaves of the plant
Perilla frutescens: an Asian garnish popularly used in sushi.

Relevant Publications:

Khandelia, H.*, Witzke, S. and Mouritsen, O.G. (2010) Interaction of Salicylate and a Terpenoid Plant
Extract with Model Membranes: Reconciling Experiments and Simulations. Biophys. J.,
doi 10.1016/j.bpj.2010.11.009

Witzke, S., Duelund, L., Pedersen, M., Kongsted, J., Mouritsen, O.G. and Khandelia, H.* (2010 Nov 11)
The inclusion of terpenoid plant extracts in lipid bilayers investigated by molecular dynamics simulations.
J. Phys. Chem. B . doi: 10.1021/jp108675b

Parry, M.J., Alakoskela, J.M., Khandelia, H., Kumar, S.A., Jaattela, M., Mahalka, A.K. and Kinnunen,
P.K. (2008) High-affinity small molecule-phospholipid complex formation: binding of siramesine to
phosphatidic acid. J. Am. Chem. Soc., doi: 10.1021/ja800516w

hydrogen-bond-between-drug-and-lipid

Image: Binding of an anticancer drug
seramesine to a secondary lipid messenger.
We showed, for the first time, that an anticancer
drug could target a secondary lipid messenger.