Development of New Target-Based Anticancer Agents from Higher Plants

本研究的目的是从高等植物中开发具有诱导细胞凋亡活性的新型靶向抗癌药物。本文研究了百合科(Liliaceae)的球果百合(Bulbinella Floribunda)、龙舌兰(Agavaceae)、山茶科(Tacca Chantrieri)、毛茅科(Ranunculaceae)的侧柏(Helleborus Orientalis)、毛茅科(Ranunculaceae)的黑毛菜(Helleborus Niger)、山梨科(Hypoxidaceae)的兰花草(Curculigo Orchioides)和菊科(Compositae)的多叶鸡骨草(Tithonia Fantrieria)的化学成分。从百合中分离得到新的苯基蒽醌类化合物、新的甾体糖苷类化合物、强心苷类化合物、植物蜕皮酮类化合物、具有环芳烃骨架的三萜类化合物以及黄酮类和倍半萜类化合物，它们分别是具有细胞毒性和抗肿瘤活性的化合物。由于从同一植物中分离出的细胞毒性化合物在结构上相互关联，因此建立了结构-活性关系。在使用多种培养的肿瘤细胞进行的小组筛选中，来自黑曲霉的一种植物蜕皮激素、一种来自鸡冠花的环丙烷三萜和一种来自杂叶草的倍半萜显示出不同的细胞毒性。一些来自utahensis的5个β-螺甾醇糖苷通过凋亡过程导致HL-60细胞死亡。

The objective of this research is to develop new target-based anticancer agents with apoptosis inducing activity from higher plants. The chemical constituents of Bulbinella floribunda (Liliaceae), Agave utahensis (Agavaceae), Tacca chantrieri (Taccaceae), Helleborus orientalis (Ranunculaceae), Helleborus niger (Ranunculaceae), Curculigo orchioides (Hypoxidaceae), and Tithonia diversifolia (Compositae) have been investigated. New phenylanthraquinone derivatives, new steroidal glycosides, cardeotonic glycosides, phytoecdysones, triterpenes with the cycloartane skeleton, and flavonoids and sesquiterpenoids were isolated from B.floribunda, A.utahensis, H.orientalis, H.niger, C.orchioides, and T.diversifolia, respectively, as cytotoxic and antitumor compounds, and their chemical structures were determined on the basis of the spectroscopic data and chemical evidence. Since the cytotoxic compounds isolated from the same plants are structurally related each other, the structure-activity relationships were established. In a panel-screening using a variety of cultured tumor cells, a phytoecdysone from H.niger, a cycloartane triterpene from C.orchioides, and a sesquiterpene from T.diversifolia showed differential cytotoxicity. Some 5β-spirostanol glycosides from A.utahensis caused the death of HL-60 cells through the apoptotic process.