Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa.
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6195-9. doi: 10.1016/j.bmcl.2012.08.005. Epub 2012 Aug 10.
Several of the Amaryllidaceae alkaloids are known for their cytotoxic properties, of which the lycorine group representatives are prominent for potent and cell line specific antiproliferative activities. As a distinct niche within the lycorine group, the phenanthridones, exemplified by narciclasine and pancratistatin, have shown much promise as remarkably selective cytotoxic agents and are presently at various stages of development, with a clinical candidate likely to appear on the market within the next decade. The crinane group of the Amaryllidaceae has also spawned several molecules, such as crinamine and haemanthamine, with promising cytotoxic activities. In the present study, the β-crinane distichamine as well as the phenanthridone narciprimine, both rare constituents of the Amaryllidaceae, are revealed as novel antiproliferative agents. Apoptosis-inducing effects are demonstrated for distichamine in human acute lymphoblastic leukemia (CEM) cells. These findings provide further insights to the structural details of the apoptosis-inducing pharmacophores resident within both series of alkaloids.
几种石蒜科生物碱以其细胞毒性而闻名，其中石蒜生物碱类代表物具有很强的细胞系特异性抗增殖活性。作为石蒜碱类中的一个独特分支，菲啶酮类，以藜芦碱和 Pancratistatin 为代表，作为非常有选择性的细胞毒性试剂具有很大的应用前景，目前正处于不同的开发阶段，在未来十年内，很可能会有临床候选药物推向市场。石蒜科的海葱烷类也产生了几种具有有前途的细胞毒性的分子，如海葱胺和血根碱。在本研究中，β-海葱烷类的二裂石蒜碱以及菲啶酮类的那可丁，都是石蒜科中罕见的成分，被证明是新型的抗增殖剂。二裂石蒜碱在人急性淋巴细胞白血病（CEM）细胞中诱导凋亡的作用。这些发现为这两类生物碱中存在的凋亡诱导药效团的结构细节提供了进一步的认识。
