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
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.