SAR studies of brasilicardin A for immunosuppressive and cytotoxic activities
SAR studies of brasilicardin A for immunosuppressive and cytotoxic activities
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DOI：
10.1016/j.bmc.2004.12.029
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发表时间：
2005-03-01
影响因子：
3.5
通讯作者：
Kobayashi, J
中科院分区：
文献类型：
--
作者：
Komatsu, K;Tsuda, M;Kobayashi, J
制备了11种具有免疫抑制和细胞毒性的三环萜类化合物brasilicardin A（1）的衍生物（5-13，15和16），并测定了其对小鼠混合淋巴细胞反应（MLR）和7种人肿瘤细胞系的抑制作用。1的17 N-甲基形式（8）在小鼠MLR中显示出最强的免疫抑制活性，而N-17的更大体积基团的诱导导致活性显著降低。化合物8还显示出对DLD-1、Lu-65、A549、K562和MOLT-4细胞的有效细胞毒性活性，而1的苄基酯（13）显示出对K562、MOLT-4和jarkat白血病细胞系的有效细胞毒性。I的17 N-乙酰基衍生物（11）选择性抑制DLD-1细胞的生长。1的甲酯（5）对K562、MOLT-4和Ball-1细胞系显示出强的细胞毒活性，后者对1、8和13具有抗性。(C)2004 Elsevier Ltd.保留所有权利。
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 I 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. (C) 2004 Elsevier Ltd. All rights reserved.