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 p38 alpha 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, p38 alpha 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-p38 alpha 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 p38 alpha and then decrease in the phospho-p38 expression.