Selective cytotoxicity of pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds.
Selective cytotoxicity of pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds.
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胰腺相关的天然杏仁核生物碱的选择性细胞毒性：两种新化合物的活性评估。
DOI：
10.1186/1475-2867-7-10
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发表时间：
2007-06-05
影响因子：
5.8
通讯作者：
Pandey, Siyaram
中科院分区：
文献类型：
--
作者：
Griffin, Carly;Sharda, Natasha;Sood, Divya;Nair, Jerald;McNulty, James;Pandey, Siyaram
从石蒜科（Amaryllidaceae，AMD）植物中提取的化合物潘克拉司他汀（Pancratistatin，PST）已被证明特异性地诱导癌细胞凋亡，而对正常细胞没有/具有最小的毒性作用。系统的合成方法表明，最小的细胞毒性药效团包括在C环中含有2，3，4-三醇单元的trans-fused B/C环系统。为了进一步探索这组化合物的结构-活性关系，我们研究了两种PST相关天然化合物AMD 4和AMD 5的抗癌功效和特异性。这两种化合物都缺乏PST的多羟基化石蒜烷元素，而是具有甲氧基取代的石蒜烷骨架。我们的研究结果表明，AMD 5具有与PST相似的功效和选择性，尽管浓度增加了10倍。有趣的是，AMD 4缺乏凋亡活性。我们的研究结果表明，在天然石蒜科生物碱中的菲酮骨架可能是一个重要的共同元素，对癌细胞的选择性;此外，甲氧基侧基的配置是负责更高的结合亲和力的目标蛋白/s，从而使一个更有效的抗癌剂。
Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton. Our results indicate that AMD5 has efficacy and selectivity similar to PST, albeit at a 10-fold increased concentration. Interestingly AMD4 lacks apoptotic activity. Our results indicate that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a significant common element for selectivity against cancer cells; furthermore, the configuration of the methoxy-side groups is responsible for higher binding affinity to the target protein/s thus making for a more efficient anti-cancer agent.
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影响因子：
5.1
作者：
PETTIT, GR;PETTIT, GR;MEEROW, AW
通讯作者：
MEEROW, AW
影响因子：
7.2
作者：
McLachlan, A;Kekre, N;Pandey, S
通讯作者：
Pandey, S
影响因子：
5.1
作者：
Pettit, GR;Eastham, SA;Bell, JA
通讯作者：
Bell, JA
影响因子：
2.7
作者：
McNulty, J;Mao, J;Boyd, MR
通讯作者：
Boyd, MR
影响因子：
4.7
作者：
RUSSO, P;POGGI, L;POMMIER, Y
通讯作者：
POMMIER, Y