Biological evaluation of structurally diverse amaryllidaceae alkaloids and their synthetic derivatives: discovery of novel leads for anticancer drug design.
Biological evaluation of structurally diverse amaryllidaceae alkaloids and their synthetic derivatives: discovery of novel leads for anticancer drug design.
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生物学评估结构上多样的汞曲霉生物碱及其合成衍生物：发现抗癌药物设计的新型铅。
DOI：
10.1055/s-0029-1185340
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发表时间：
2009-04
期刊：
影响因子：
2.7
通讯作者：
Kornienko A
中科院分区：
文献类型：
--
作者：
Evidente A;Kireev AS;Jenkins AR;Romero AE;Steelant WF;Van Slambrouck S;Kornienko A
本研究对石蒜科生物碱及其衍生物进行了体外抗增殖、诱导凋亡和抗侵袭活性的评价。石蒜碱型、石蒜氨酸型、tazettine型、crinine型和水仙碱型5类石蒜科生物碱及其衍生物共29种。每种测试化合物的抗增殖特性与文献中报道的那些一致，而amarbellisine的高效力是首次报道。还发现，除了恩格列明、阿马尔贝里斯碱和马匹斯汀之外，有效化合物的抗增殖作用是促增殖介导的。因此，Jurkat细胞中的凋亡由那昔克拉新、那昔克拉新四乙酸酯、C10 b-R-羟基潘生丁、顺式-二氢那昔克拉新、反式-二氢那昔克拉新、石蒜碱、1-O-乙酰石蒜碱、石蒜碱-2-酮、假石蒜碱和血红胺触发。除水仙碱、石蒜碱和血红胺外，这些化合物的细胞凋亡诱导性质均为首次报道。I型胶原侵袭试验显示与N-甲基石蒜碱碘化物、马豆碱、氯立维明、丁苯那明和那昔克拉新四乙酸盐相关的有效抗侵袭特性，所有这些都在无毒浓度下进行了测试。丁法那明的抗侵袭活性特别有希望，因为这种生物碱即使在高得多的剂量下对细胞也没有毒性。这项工作导致了几个新的抗癌药物设计的线索的识别。
Twenty nine Amaryllidaceae alkaloids and their derivatives belonging to five most common groups, including lycorine-, lycorenine-, tazettine-, crinine-, and narciclasine-types, were evaluated for antiproliferative, apoptosis inducing and antiinvasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis-mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine and haemanthamine, the apoptosis inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent antiinvasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The antiinvasive activity of buphanamine is particularly promising since this alkaloid is not toxic to cells even at much higher doses. This work has resulted in identification of several novel leads for anticancer drug design.
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影响因子：
8.8
作者：
Barthelmes HU;Niederberger E;Roth T;Schulte K;Tang WC;Boege F;Fiebig HH;Eisenbrand G;Marko D
通讯作者：
Marko D
影响因子：
3.8
作者：
EVIDENTE, A;CICALA, MR;ARRIGONI, O
通讯作者：
ARRIGONI, O
影响因子：
3.8
作者：
ABOUDONIA, AH;ABIB, AA;SCOPA, A
通讯作者：
SCOPA, A
影响因子：
4.8
作者：
Dumont, Patrick;Ingrassia, Laurent;Kiss, Robert
通讯作者：
Kiss, Robert
影响因子：
3.8
作者：
Evidente, A;Andolfi, A;Motta, A
通讯作者：
Motta, A