Keawpradub N, Eno-Amooquaye E, Burke P J, Houghton P J
Department of Pharmacy, King's College London, U.K.
Planta Med. 1999 May;65(4):311-5. doi: 10.1055/s-1999-13992.
Thirteen indole alkaloids isolated from the root bark of Alstonia macrophylla and a semisynthetic bisindole O-acetylmacralstonine have been assessed for cytotoxic activity against two human lung cancer cell lines, MOR-P (adenocarcinoma) and COR-L23 (large cell carcinoma), using the SRB assay. Pronounced cytotoxic activity was exhibited by the bisindoles on both cell lines. This suggests that, in comparison with the corresponding monomeric indoles, at least part of both the ring systems present in the bisindoles is essential for cytotoxic activity. The potent alkaloids were further tested against a human normal cell line (breast fibroblasts) and other human cancer cell lines including StMI1 1a (melanoma), Caki-2 (renal cell carcinoma), MCF7 (breast adenocarcinoma), and LS174T (colon adenocarcinoma). The bisindoles O-acetylmacralstonine, villalstonine and macrocarpamine were found to possess pronounced activity against cancer cell lines with IC50 values in the range of 2-10 microM, with no discernible cell-type selectivity. However, O-acetylmacralstonine displayed discernibly less toxicity against the normal breast fibroblasts.
从大叶鸡骨常山根皮中分离出的13种吲哚生物碱以及一种半合成双吲哚O - 乙酰基鸡骨常山碱，已通过SRB分析法评估了它们对两种人肺癌细胞系MOR - P（腺癌）和COR - L23（大细胞癌）的细胞毒性活性。双吲哚对这两种细胞系均表现出显著的细胞毒性活性。这表明，与相应的单体吲哚相比，双吲哚中存在的两个环系统至少部分对于细胞毒性活性至关重要。对这些强效生物碱进一步针对人正常细胞系（乳腺成纤维细胞）以及其他人类癌细胞系进行了测试，包括StMI1 1a（黑色素瘤）、Caki - 2（肾细胞癌）、MCF7（乳腺腺癌）和LS174T（结肠腺癌）。发现双吲哚O - 乙酰基鸡骨常山碱、鸡骨常山宁碱和大果荚蒾胺对癌细胞系具有显著活性，IC50值在2 - 10微摩尔范围内，且没有明显的细胞类型选择性。然而，O - 乙酰基鸡骨常山碱对正常乳腺成纤维细胞的毒性明显较小。
