长春花吲哚萜类生物碱代谢途径研究进展

长春花(Catharanthus roseus(L.)G.Don.)含有130余种生物碱,既是抗癌药物长春碱和长春新碱的唯一植物来源,也是研究吲哚萜类生物碱代谢途径的模式植物。生成长春花生物碱的前体环烯醚萜主要来源于2-C-甲基-D-赤藓醇4-磷酸途径(MEP),甲羟戊酸途径(MVA)可能在此过程中起辅助作用。吲哚生物碱代谢途径受茉莉酸甲酯正调控。文多灵途径过去被认为在长春花悬浮细胞中没有文多灵产生,而目前的研究发现文多灵在长春花C20hi细胞中可以微量合成。文章对近年来长春花吲哚生物碱代谢途径及部分关键酶研究进展进行了综述。     

长春花生物碱类衍生物及靶向前药研究进展

[摘要]长春花生物碱作为一类抗有丝分裂药物,能够抑制微管聚合并诱导聚合的微管蛋白解聚。目前主要从两方面对长春碱类药物进行结构修饰：一是依据长春花生物碱类药物的构效关系,对其活性中心进行修饰,合成一系列长春碱类衍生物,以期寻找到具有更高药理活性、更低毒性和更广抗肿瘤谱的长春花生物碱类药物;二是在保证药理活性的前提下,在一些非活性位点引入靶向基团(特异性寡肽、单克隆抗体及叶酸等),合成一系列长春花生物碱类衍生物靶向前药,以期降低长春碱类药物的毒副作用,提高其治疗指数。文中综述了长春花生物碱类衍生物和长春花生物碱类药物靶向前药的研究进展。     

长春花化学成分和药理作用研究进展

长春花属植物是原产于非洲东海岸的野生花卉,现已广泛分布于世界各地.长春花含有萜类生物碱、二聚吲哚生物碱、单吲哚生物碱等多种生物碱类活性成分和黄酮类成分.近年来长春花中单体成分或结构修饰物作为药物被广泛用于治疗多种癌症、糖尿病、高血压及何杰金氏病.综述了近年来对长春花生物碱类和药理活性的研究进展,为更好地开发、利用长春花...     

长春花生物碱生物合成的分子机理

综述了近几年来国内外关于长春花生物碱生物合成途径、相关基因表达与调控的分子机理以及影响因素，并探讨了进一步研究的方向。     

长春花培养细胞中阿玛碱提取及高效液相色谱定量测定

建立固相快速提取及高效液相色谱测定长春花细胞培养中可玛碱的方法，并用此方法对三种长春花细胞系Ｃ２０ｈｉ，Ｃ２０Ｄ和Ｃ２０的生物碱合成能力做了比较。研究发现，提取液ｐＨ值在３．５５－８．０范围内阿玛碱的回收率均为９５％－１０５％。荧光检测器的灵敏度可以达到０．４５ｎｇ，进样量在５－７５ｎｇ之间时与峰面积呈线性关系，三种长春花细胞系的生物碱合成能力大小依次是Ｃ２０ｈｉ〉Ｃ２０Ｄ〉Ｃ２０     

长春花组织培养研究进展

长春花含有100多种吲哚类生物碱,具有抗肿瘤、降血压等多种生物活性,有较高的药用价值,但是含量偏低。长春花组织培养可从提高繁殖系数、调控次生代谢产物的累积等来提高长春花生物碱类成分含量。本文就外植体和培养基的选择、药用成分累积的影响因素、悬浮细胞培养应用、影响毛状根因素和基因工程技术应用等方面,综述了长春花组织培养的主要研究进展,为进一步开发利用长春花药物资源提供参考。     

长春花中抗癌生物碱研究的最近进展

自从发现夹竹桃科植物长春花(Catha-ranthns roseus)中某些生物碱具有抗癌活性之后,十余年来国外对这一属植物所含生物碱进行了大量的分离、结构测定、化学合成和药理研究工作。迄今已从长春花中分     

抗肿瘤药物长春氟宁

长春氟宁为第3代长春花生物碱双氟化半合成衍生物,对包括尿路上皮移行细胞癌（TCCU）在内的多种实体瘤有抗癌活性,且与其他长春花生物碱衍生物相比,其抗癌活性更强、更安全。一项Ⅲ期临床研究的多因素分析显示：在最佳支持疗法（BSC）的基础上加用长春氟宁能明显提高TCCU患者总体生存率。     

GC-MS分析长春花中的主要吲哚生物碱

在80年代,大量的研究致力于以细胞和组织培养的方法生产长春花中具有药物作用的吲哚生物碱,研究的主要目标是长春新碱和长春碱,它们被用于癌症化疗并作为一些半合成衍生物的前体。上述双吲哚生物碱是由长春花碱(catharanthine)和文朵灵(vindo-line)生物合成的。此外长春花还含有柯南类生物碱阿吗里新(ajmalicine)。由于商业上提供的熔融石英毛细管气相色谱柱固定相有广泛的选择余地.大大扩展了GC分析包括胺和生物碱类在内的不同药物和天然化合物的应用范围。本文研究了以GC-MS方法,通过简单的纯化步骤,同时直接测定长春花中的文朵灵     

天然药物

草本蔓长春花营养器官的解剖构造与生物碱的定位草本蔓长春花(Vinca herbacea W.et K.)为夹竹桃科多年生的草本植物。它含有利血平等多种吲哚类生物碱。它的地上部分可作为治疗高血压病的药物长春花胺(Vincamine)的原料。由于有关其生药解剖资料的文献很不完全,对其各组织中生物碱综合定位的资料更为缺乏,因此,本文就这些方面进行了研究。实验所用的标本系在开花期分别采集野生及栽培品种的根、根茎、茎与叶,经干燥、固定后用冰冻切片机切片。并用一般生物碱沉淀剂于荧光显微镜下观察,进行生物碱的定位。     

The Catharanthus alkaloids: pharmacognosy and biotechnology

The Catharanthus (or Vinca) alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development. Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine, Catharanthus roseus became one of the best-studied medicinal plants. Consequently it developed as a model system for biotechnological studies on plant secondary metabolism. The aim of this review is to acquaint a broader audience with the recent progress in this research and with its exciting perspectives. The pharmacognostical aspects of the Catharanthus alkaloids cover botanical (including some historical), phytochemical and analytical data. An up-to-date view on the biosynthesis of the alkaloids is given. The pharmacological aspects of these alkaloids and their semi-synthetic derivatives are only discussed briefly. The biotechnological part focuses on alternative production systems for these alkaloids, for example by in vitro culture of C. roseus cells. Subsequently it will be discussed to what extent the alkaloid biosynthetic pathway can be manipulated genetically ("metabolic engineering"), aiming at higher production levels of the alkaloids. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast. Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off. It is clear that many interesting results can be expected when more genes become available.     

Distribution and accumulation of alkaloids in Catharanthus roseus G. Don during development

Pattern of the total alkaloids distribution and accumulation in Catharanthus roseus G. Don was investigated during six different stages of flowering and fruiting. The highest concentration of alkaloids (mg perivine/g dry weight) was found in the roots at the start of flowering and the minimum in the stems during full fruiting stage; the rate of alkaloidal accumulation in the leaves, stems and roots tended to decrease during fruit maturation. The most active stage of alkaloidal biosynthesis was at the start of flowering in all vegetative organs. The maximum dry weights of leaves, stems and roots were obtained during the start of fruiting. The weights of flowers and fruits were relatively very small during different developmental stages. Harvesting Catharanthus roseus should best be carried out at the full-flowering stage to obtain the optimum yield of total alkaloidal content of leaves, stems and roots (as mg perivine/total dry weight of each organ per plant).     

Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don) XXXVI: Isolation and characterization of new dimeric alkaloids.

In a continuing effort to study thoroughly the alkaloids of Catharanthus roseus, new dimeric alkaloids were isolated and characterized. Structures are proposed for leurocolombine and vinamidine based on UV, IR, PMR, high-resolution mass spectrometry, and CMR. Pseudovincaleukoblastine diol was identified by PMR and mass spectrometry. Leurocolombine exhibited antimitotic activity and marginal antitumor activity against the Ridgeway osteogenic sarcoma.     

Alkaloid Production in Catharanthus roseus cell cultures VIII

A cell line of Catharanthus roseus (L.) G. Don coded PRL # 200, was characterized with respect to its biosynthetic capabilities for indolealkaloids, in particular catharanthine, in suspension cultures. Other alkaloids isolated are vallesiachotamine isomers, ajmalicine, h?rhammericine, h?rhammerinine, vindolinine, 19-epivindolinine and strictosidine lactam.     

长春花脱乙酰氧基文多灵-4-羟化酶基因启动子的克隆与生物信息学分析

通过基因组步行技术克隆到长春花脱乙酰氧基文多灵-4-羟化酶基因上游905bp启动子序列,生物信息学分析发现该序列中存在多个与光照诱导有关的顺式元件,同时也发现一个与长春花特异的顺式作用元件JERE类似的短序列,推测该序列是茉莉酸诱导途径中转录因子ORCA3的特异结合位点。     

Two pairs of epimeric indole alkaloids from Catharanthus roseus

Two pairs of epimeric indole alkaloids (1- 4) with a chlorine atom were isolated from the aerial part of Catharanthus roseus. Their structures were established on the basis of the spectroscopic data including UV, IR, HRESIMS, NMR, and X-ray diffraction analyses. The cytotoxic activities of 1-4 against the HepG2 cell line were evaluated.     

Three new terpenoid indole alkaloids from Catharanthus roseus

Three new terpenoid indole alkaloids, vidolicine (1), normacusine B N-oxide (2), and lochnerine N-oxide (3), together with seven known ones (4-10), were isolated from whole plants of Catharanthus roseus. Their structures were elucidated by spectroscopic methods (NMR, MS, UV, and IR). Cytotoxic activities of these isolates (1-10) were evaluated, but only compound 8 was active against HL-60, SMMC-7721, and A549 cell lines.