Antiproliferative Activity of Diarylheptanoids from the Seeds of Alpinia blepharocalyx

The 95% EtOH extract of the seeds of Alpinia blepharocalyx (Zingiberaceae) showed significant antiproliferative activity towards human HT-1080 fibrosarcoma and murine colon 26-L5 carcinoma cells. Chemical investigation of the extract led to the isolation of forty-four new (1—44) and one known (45) diarylheptanoids, eleven phenolic compounds (46—56) together with β-sitosterol glucoside (57). Almost all the isolated compounds showed significant antiproliferative activity in a concentration-dependent manner. Among the compounds, epicalyxin F (17) exhibited the most potent activity against the proliferation of colon 26-L5 carcinoma cells with an ED50 value of 0.89 μM, while calyxin B (2) exhibited the most potent activity against human HT-1080 fibrosarcoma cells with an ED50 value of 0.69 μM. Moreover, calyxins B (2) and K (11), epicalyxins F (17), I (20) and K (22), 6-hydroxycalyxin F (25), blepharocalyxin B (27) and mixtures of 7 and epicalyxin G (18) and of calyxin J (10) and epicalyxin J (21) possessed more potent activity than a clinically used anticancer drug, 5-fluorouracil, towards HT-1080 fibrosarcoma cells. Analysis of the structure activity relationship suggested that the position of the attachment of a chalcone or a flavanone moiety does not affect the activity, although their presence in association causes a substantial enhancement of the antiproliferative activity. Moreover, the conjugated double bond of the chalcone moiety and the phenolic hydroxyl group potentiate the antiproliferative activity of the compounds.