Development of New Target-Based Anticancer Agents from Higher Plants

本研究旨在从高等植物中开发具有诱导细胞凋亡活性的靶向抗癌药物。本文研究了百合科、龙舌兰科、金缕莲科、东方龙舌兰科、黑龙舌兰科、凤仙花科、金针兰科、金针兰科、金针兰科、金针兰科等植物的化学成分。从鸢尾花、鸢尾花、东方花、黑花花、兰花花和金合花中分别分离到新的苯蒽醌衍生物、新的甾体苷、心强苷、植物蜕皮酮、环ar烷骨架三萜、类黄酮和倍半萜类化合物，并根据光谱数据和化学证据确定了它们的化学结构。由于从同一种植物中分离的细胞毒性化合物在结构上具有亲缘关系，因此建立了构效关系。在使用多种培养的肿瘤细胞进行的小组筛选中，一种来自黑草的植物蜕皮素、一种来自兰花的环ar烷三萜和一种来自金合春的倍半萜显示出不同的细胞毒性。乌塔亨菌中部分5β-螺甾醇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.