SAR studies of brasilicardin A for immunosuppressive and cytotoxic activities.
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 17N-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 17N-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.
Komatsu
Kazusei
K
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Tsuda
Masashi
M
Tanaka
Yasushi
Y
Mikami
Yuzuru
Y
Kobayashi
Jun'ichi
J
D000617:Aminoglycosides / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000970:Antineoplastic Agents; C118259:brasilicardin A