Aim and Objective: The brominated tyrosine alkaloids which have broad biological activity are
commonly found in marine sponges of the Verongida order, However, with the discovery of itampolin A and B
from the Madagascan sponge, Iotrochota purpurea, a plurality of brominated tyrosine derivatives have been
found in the sponge Iotrochota purpurea. This study was undertaken to study antitumor activity of itampolin A
and to explore the possible mechanism.
Material and Method: The total synthesis of itampolin A was first performed to obtain purified brominated
tyrosine alkaloid, then the cytotoxicities of itampolin A were evaluated by MTT method against H460 and
A549 cells. To explore the possible mechanism, potential target identification by latest integrated pharmacophore
matching platform of itampolin A was carried out using PharmMapper Server. Finally, expression of
phospho p38α protein was studied using the western blot analysis.
Results: Itampolin A and enantiomer of itampolin A were obtained, the latter is a novel compound named (-)-
itampolin A, which exhibited significant anticancer activity in the biological tests. After potential target identification
by latest integrated pharmacophore matching platform of itampolin A, p38α was screened out as the
target protein. Then in the Western-blot analysis, it was proposed that (-)-itampolin A inhibited tumor cells by
reducing the phospho-p38α expression.
Conclusion: (+)-itampolin A was a brominated tyrosine derivative, isolated from the sponge Iotrochota purpurea.
For the first time, the total synthesis of itampolin A was achieved. The enantiomer, (-)-itampolin A was
found to show inhibitory activity on the cultured lung cancer A549 cells. The underlying anticancer mechanisms
may be associated with its binding to p38α and then decrease in the phospho-p38 expression.