SAR studies of brasilicardin A for immunosuppressive and cytotoxic activities

Abstract

Eleven derivatives ( 5– 13, 15, and 16) of an immunosuppressive and cytotoxic tricyclic terpenoid, brasilicardin A ( 1), were prepared and assayed for inhibitory effects to the mouse mixed lymphocyte reaction (MLR) and seven human tumor cell lines. The 17 N-methyl form ( 8) of 1 showed the most potent immunosuppressive activity in mouse MLR, while induction of more bulky group for N-17 resulted in significant decrease of the activity. Compound 8 also showed potent cytotoxic activity against DLD-1, Lu-65, A549, K562, and MOLT-4 cells, while the benzyl ester ( 13) of 1 exhibited potent cytotoxicity against K562, MOLT-4, and jarkat leukemia cell lines. The 17 N-acetyl derivative ( 11) of 1 selectively inhibited the cell growth of DLD-1 cells. The methyl ester ( 5) of 1 showed potent cytotoxic activity against K562, MOLT-4, and Ball-1 cell lines, the last of which was resistant to 1, 8, and 13.