The first total synthesis and biological evaluation of marine natural products ma'edamines A and B.

ABSTRACT

We have developed the first total syntheses of marine natural products ma'edamines 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, ma'edamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 (IC(50) 7.9 and 10.3 µM, respectively), breast cancer cell line MCF-7 (IC(50) 6.9 and 10.5 µM, respectively) and human lung adenocarcinoma cell line A549 (IC(50) 12.2 and 15.4 µM, respectively). The apoptotic effect of ma'edamines was confirmed by comet assay. Hence ma'edamines are likely to be useful as leads for development of a new class of anti-cancer agents.