The first total synthesis and biological evaluation of marine natural products maaedamines A and B

We have developed the first total syntheses of marine natural products maaedamines A (18) and B (20). Structurally, they contain a pyrazine-2-(1H)-one core and were screened for antiproliferative activity on several cancer cell lines. Out of the six cell lines tested, maaedamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 (IC50 7.9 and 10.3 mu M, respectively), breast cancer cell line MCF-7 (IC50: 6.9 and 10.5 mu M, respectively) and human lung adenocarcinoma cell line A549 (IC50: 12.2 and 15.4 mu M, respectively). The apoptotic effect of maaedamines was confirmed by comet assay. Hence maaedamines are likely to be useful as leads for development of a new class of anti-cancer agents.