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ABSTRACT: The MeOH extract of the Netherlands propolis showed promising antiproliferative activity toward highly liver-metastatic murine colon 26-L5 carcinoma with an EC(50) value of 3.5 microg/ml. Further, antiproliferative activity-guided purification of the MeOH extract led us to isolate four flavonoids (1-4), seven cinnamic acid derivatives (5-11) and two new glycerol derivatives (12, 13), whose structures were elucidated on the basis of spectral analysis. The isolated compounds were tested for their antiproliferative activity against murine colon 26-L5, murine B16-BL6 melanoma, human HT-1080 fibrosarcoma and human lung A549 adenocarcinoma cell lines. The benzyl (9), phenethyl (10) and cinnamyl caffeates (11) possessed potent antiproliferative activities with EC(50) values of 0.288, 1.76 and 0.114 microM, respectively, toward colon 26-L5 carcinoma. These caffeates were considered to be active constituents of the Netherlands propolis in their antiproliferative activity. The antioxidative activity of these caffeates may play an important role in their antiproliferative activities.
Toyama Medical and Pharmaceutical UniversityТояма, Toyama, Japan