植物组织培养中甾族化合物及其代谢

用植物愈伤组织及悬浮培养研究甾族化合物已获得一定的成就。基本上可通过三条途径来研究植物组织培养中甾族化合物的生物合成及其代谢变化:(1)分离和检出愈伤组织及悬浮培养所产生的甾族化合物;(2)应用     

1-脱氧-D-木酮糖醇-5-磷酸还原异构酶（DXR）作为新的药物靶点的研究进展

植物、藻类和细菌等可利用2C-甲基-D-赤藓糖醇．4．磷酸（MEP）途径生物合成类异戊二烯前体异戊酰焦磷酸（IPP）及其异构体二甲烯丙基焦磷酸（DMAPP）等生长所必须的前体,因此MEP途径作为除草剂、抗菌药物和抗疟疾药物的药物靶点可用于新药开发。其中MEP途径中的第二个酶1-脱氧-D-木酮糖醇-5-磷酸还原异构酶（DXR）是研究最为广泛的靶点,膦胺霉索即为该酶的抑制剂。本综述主要介绍MEP途径、DXR及其抑制剂的研究进展。     

达哪唑衍生物的合成

黄体酮是维持正常妊娠所必需的孕激素,一些能抑制黄体酮生物合成或与黄体酮受体有很强结合力的化合物都有可能终止早期妊娠与导致流产。已知甾体[2,3 d]异恶唑类如达哪唑(danazol),azastene和甾体-2α-氰基-3-酮类如cyanoketone,trilostane(4),epos-     

桦木属植物三萜类化合物研究进展

植物次生代谢产物是天然药物的重要来源。桦木属植物具有丰富的药用价值,药理作用机制复杂,这与其中的三萜类化合物具有密不可分的关系。桦木属植物三萜类化合物主要分为达玛烷型、奥克梯隆型、齐墩果烷型、羽扇豆烷型和环阿屯烷型;桦木属植物提取物具有抗肿瘤、抗炎、抗氧化、抗菌等多种活性;桦木属植物三萜类化合物的生物合成途径自2,3-氧化鲨烯之后根据环氧角鲨烯环化酶的不同分为达玛烯二醇Ⅱ、羽扇豆醇、环阿屯醇和香树酯四个分支。本文对桦木属植物三萜类化学成分、药理活性和生物合成途径解析三个方面进行了综述,以期为利用桦木属植物三萜类化合物进行新药研发及利用合成生物学方法在微生物细胞工厂中生产这类化合物提供参考。     

三宝木枝条抗菌活性成分的分离与鉴定

目的研究三宝木(Trigonostemon chinensis Merr.)枝条的化学成分。方法采用多种柱色谱技术进行分离纯化,通过理化性质和波谱数据分析鉴定化合物的结构,采用滤纸片琼脂扩散法测定化合物抗菌活性。结果从三宝木枝条乙醇提取物的乙酸乙酯萃取物中分离得到了12个已知化合物,经波谱分析鉴定为松脂醇(1)、(+)-de-4″-O-methylmagnolin(2)、丁香脂素(3)、nitidanin(4)、臭矢菜素A(5)、6-deoxyjacareubin(6)、巴西红厚壳素(7)、豆甾-4,22-二烯-3-酮(8)、3β-羟基豆甾-5-烯-7-酮(9)、豆甾-4-烯-3-酮(10)、正十八酸(11)、β-谷甾醇(12)。结论 12个化合物均为首次从该植物中分离得到,其中,化合物2、4、5、8、9、10是首次从该属植物中分离得到。初步抗菌活性结果表明化合物7对金黄色葡萄球菌、烟草青枯菌具有抑制活性。     

药用植物中鲨烯环氧酶基因的研究进展

鲨烯环氧酶(SE)存在于内质网的微粒体中,在鲨烯转变为环氧化鲨烯的生物过程中作为生物催化剂起催化作用。而环氧化鲨烯是从鲨烯生成环阿屯醇、香树素、羊毛甾醇等的过程中重要的中间产物。SE的活性决定了环氧化鲨烯的生物合成的效率,继而,以环氧化鲨烯作为前体的各类甾体皂苷、三萜皂苷、甾醇等化合物的生物合成也随之受其影响,后续产物的产量取决于它的含量和活性。因此SE被认为是甾体皂苷生物合成途径中的一个非常重要的调控酶,已在多种植物中克隆出并进行了初步功能鉴定。该文概述几个重要药用植物的SE基因的克隆及原核表达,为从其他药用植物中克隆SE基因提供一定的参考依据及方法思路。     

莲子草属植物的化学成分及生物活性研究进展

目的对苋科莲子草属植物的化学成分和生物活性作一综述。方法按照化合物的结构类型对莲子草属植物的化学成分进行分类综述 ,并且对其主要的生物活性进行总结。结果莲子草属植物含有多种活性成分 ,主要有三萜类、甾体类、黄酮类、有机酸类等化合物 ,他们具有抗菌、抗病毒等生物活性。结论为莲子草属植物的研究与开发提供了参考。     

红树植物老鼠簕中的甾醇成分

目的系统研究红树植物老鼠簕Acanthus ilicifolius的化学成分。方法利用硅胶柱色谱、Sephadex LH-20凝胶色谱、HPLC高效液相色谱等方法分离纯化化合物,根据波谱数据和理化常数确定其结构。结果与结论从老鼠簕甲醇提取物的石油醚部位分离鉴定了9个化合物,分别是豆甾-4-烯-3-酮(1),豆甾-4,22-二烯-3-酮(2),麦角甾-4-烯-3-酮(3),豆甾-4-烯-3,6-二酮(4),豆甾-4,22-二烯-3,6-二酮(5),豆甾-4,22-二烯-6β-羟基-3-酮(6),6β-羟基-豆甾-4-烯-3-酮(7),3β-羟基-豆甾-5,22-二烯-7-酮(8),3β-羟基-豆甾-5-烯-7-酮(9)。其中,化合物4～8为首次从该植物中分离得到。体外细胞毒筛选实验表明,化合物2、4和9具有中等的细胞毒活性。     

芸香科柠檬苦素类化合物及其生物活性研究进展

柠檬苦素类化合物是由大戟烷或甘遂烷型三萜衍生而来的一类高度氧化的四降三萜类化合物,是芸香目主要特征的化学成分,主要存在于芸香科和楝科植物中,叶柄花科和苦木科等亦有分布。芸香科中柠檬苦素类化合物以苷元和糖苷2种形式存在。这类化合物具有明显抗癌和抗菌等生物活性,近年来的研究集中在其化学结构、生物合成和生物活性等方面。本文对从芸香科植物中分离得到的柠檬苦素类化合物的化学结构、生物合成途径及生物活性等方面的研究现状进行综述。     

黑鳗藤属植物C_(21)甾体苷类化学成分及其免疫作用研究进展

C21甾体苷是一类重要的活性成分,具有抗肿瘤、调节免疫等多方面药理作用,近年来已成为研究热点。黑鳗藤属植物富含各种C21甾体苷类成分,目前已从该属植物中分离得到大量C21甾体化合物。现综述国内外对黑鳗藤属植物C21甾体类成分及其免疫作用的研究进展。     

葡萄细胞中白藜芦醇生物合成的研究进展

白藜芦醇是1种含有芪类结构的植物多酚化合物,具有抗氧化、抗菌、抗癌等多种生物活性;葡萄是提取白藜芦醇的主要植物资源;介绍葡萄中白藜芦醇含量的品种及其分布差异;综述葡萄细胞的培养方式和利用葡萄细胞生物技术生产白藜芦醇的技术的文献,探讨葡萄中白藜芦醇的生物合成途径及其基因调控等方面的研究进展,为白藜芦醇的生物技术生产提供理论参考.     

Antifolate agents: a patent review (2006 - 2010)

INTRODUCTION: For > 50 years, drugs targeting the folate pathway have significantly impacted disease treatment as anticancer, antimicrobial and immunomodulatory agents. The discovery of novel antifolate agents with improved properties and superior activities remains an attractive strategy, both in academia and the pharmaceutical industry. AREAS COVERED: This review surveys the patent literature from 2006 to 2010 for small molecule inhibitors of enzymatic targets in the folate biosynthetic pathway. EXPERT OPINION: The pursuit of antifolates as anticancer and antimicrobial agents continues to be an active area of research. New patent disclosures reveal novel antifolate scaffolds, antifolates with improved drug-like properties and new strategies to effectively target cancer cells. The continued use of high resolution structural information has guided the discovery of several compounds. Owing to the need for high levels of potency and selectivity, especially in targeting pathogenic species, the use of high resolution crystal structures remains an important tool to guide the design of novel antifolates. Interestingly, the patents disclosing novel compounds were ones where X-ray crystallography was an integral component of the design process. Finally, a variety of new structures have been reported that may play an important role in the future development of therapeutic antifolates.     

Developmental aspects of hepatic heme biosynthetic capability and hematotoxicity

δ-Aminolevulinic acid (ALA) synthetase is considered to be rate-limiting in heme biosynthesis in normal adult mammalian liver. However, under certain pharmacological or pathological circumstances, other enyzmes of the heme biosynthetic pathway have been shown to be limiting in this process. In the current studies, the developmental patterns of ALA dehydratase, uroporphyrinogen I synthetase and heme synthetase were measured in rat liver, and the potential influence of these enzymes on heme biosynthetic capability under various conditions in adult, neonatal and fetal liver was assessed. In addition, a comparison of the activities of these enzymes with those of ALA synthetase was made as a means of assessing the relative influence of hematotoxic agents on hepatic heme biosynthetic capability at different stages of development.     

Antifolate agents: a patent review (2006 – 2010)

Introduction: For > 50 years, drugs targeting the folate pathway have significantly impacted disease treatment as anticancer, antimicrobial and immunomodulatory agents. The discovery of novel antifolate agents with improved properties and superior activities remains an attractive strategy, both in academia and the pharmaceutical industry.

Areas covered: This review surveys the patent literature from 2006 to 2010 for small molecule inhibitors of enzymatic targets in the folate biosynthetic pathway.

Expert opinion: The pursuit of antifolates as anticancer and antimicrobial agents continues to be an active area of research. New patent disclosures reveal novel antifolate scaffolds, antifolates with improved drug-like properties and new strategies to effectively target cancer cells. The continued use of high resolution structural information has guided the discovery of several compounds. Owing to the need for high levels of potency and selectivity, especially in targeting pathogenic species, the use of high resolution crystal structures remains an important tool to guide the design of novel antifolates. Interestingly, the patents disclosing novel compounds were ones where X-ray crystallography was an integral component of the design process. Finally, a variety of new structures have been reported that may play an important role in the future development of therapeutic antifolates.     

The age-related discrepancy in the effect of neuropeptide Y on select catecholamine biosynthetic enzymes in the adrenal medulla and hypothalamus in rats

The elevated levels of circulating catecholamines (CAs) with age may be related to the increased expression of CA biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine β hydroxylase (DβH) in the adrenal medulla of senescent compared with younger animals. Neuropeptide Y (NPY) is co-synthesized and co-released with CAs in the adrenal medulla. NPY inhibits the stimulated secretion of CAs, however, its role in regulation of the genes encoding CA biosynthetic enzymes is not clear. We hypothesized that NPY up-regulates TH, DβH and NPY expression in the adrenal medullae of young and old Fischer-344 rats. NPY increased mRNA expression of TH, DβH, NPY and also enhanced TH protein level in the adrenal medullae of young rats by 50%, 35%, 45% and by 20%, respectively. We also examined the effect of NPY on TH and NPY mRNA in the hypothalamus. Basal expression of TH mRNA was decreased in the hypothalamus with age. DNA binding activities of activator protein-1 and cAMP response element binding protein were also augmented only in the young by 140% and 125%, respectively. We conclude that NPY stimulates the CA biosynthetic pathway in the adrenal medulla and positive auto-regulation of NPY might be involved in this process. The stimulatory effect of NPY on adrenomedullary CA biosynthetic pathway is blunted with age.     

Exposure to toxic agents: the heme biosynthetic pathway and hemoproteins as indicator

The heme biosynthetic pathway is closely controlled by levels of the end product of the pathway, namely, heme, and porphyrins are normally formed in only trace amounts. When control mechanisms are disturbed by xenobiotics, porphyrins accumulate and serve as a signal of the interaction between a xenobiotic and the heme biosynthetic pathway. For example, an increase in erythrocyte protoporphyrin is a useful measurement for early detection of exposure to lead and porphyrinuria was an early manifestation of a hexachlorobenzene-induced porphyria in Turkey. In recent years a variety of additional xenobiotics has been shown to interact with the heme biosynthetic pathway, namely, halogenated aromatic hydrocarbons, pesticides, sulfides, and a variety of metals. Moreover, different xenobiotics (e.g., dihydropyridines and compounds containing unsaturated carbon-carbon bonds) interact with the prosthetic heme of cytochrome P-450 forming novel N-alkylporphyrins.     

Recent progress on the lupine alkaloids in leguminous plants growing mainly in Japan

The existence of the lupine alkaloids in leguminous plants mainly growing in Japan has been thoroughly ascertained, and 106 kinds of lupine alkaloids, including 51 kinds of novel lupine-type alkaloids, have been isolated and characterized from 28 species belonging to the 9 genera of leguminous plants (Table 1). Among them (e.g. Fig. 1-2), a number of unusual types of alkaloids (e.g. Fig. 2) may be regarded as possible metabolites of the lupine alkaloids that coexist in the same plant, such as (+)-kuraramine-type, (-)-mamanine-type (Fig. 3), (-)-tsukushinamine-type (Fig. 5) and (+)-hupeol-type (Fig. 7) alkaloids, or as products of alternative biosynthetic pathway, such as tashiromine-type and (-)-camoensidine-type alkaloids in the Maackia species. The biosynthetic pathways (Fig. 8) by enzymes (Fig. 9) and some of biological activities (e.g. Table 2) of the lupine alkaloids have also been presented. The leguminous plants that accumulate the common lupine alkaloids may be divided into three main groups: plants which produce the matrine, the cytisine/sparteine, and the lupinine-type alkaloids. In addition, the Maackia species and a few other species produce rare bases. Some of more detailed chemical properties of the lupine alkaloids that have been isolated and studied in our laboratory, including a newly proposed biosynthetic pathway, biotechnological studies, a summary of biological activities, and a discussion of chemotaxonomic aspects of the leguminous plants which accumulate lupine alkaloids, have been reviewed by authors in English papers shown in References 1, 55, 65, and also reviewed by one of the authors (I.M.) in a Japanese papers shown in Ref. 66, in which many aspects of the active research history on (+)-matrine and its relatively alkaloids since 1892 in Japan are described.     

Chemical Constituents and Preliminary Antimalarial Activity of Humiria balsamifera

From stems and leaves of Humiria balsamifera St. (Aubl.) Hill (Humiriaceae) were isolated 6 triterpenes [arjunolic acid, 2β,3α-dihydroxy-D:A-friedooleanane, friedelin, α- and β-amyrins and lupeol], a flavonol (quercetin), an isocoumarin (bergenin) a diterpene (phytol), and 2 phytosteroids (sitosterol and stigmasterol)]. Three sesquiterpenoids [caryophyllene oxide (0.9%), humulene epoxide II (0.3%) and trans-isolongifolenone (0.6%)], a diterpene [phytol (29.4%)] and four aliphatic esters [methyl tetra- (0.3%), hexa- (26.6%) and octadecanoate (0.3%), and ethyl tetradecanoate (26.9%)] were identified by GC/MS. Some crude extracts, arjunolic acid and bergenin, were screened in vivo and/or in vitro for their antimalarial activities against a chloroquine resistant strain. Structures of all isolated compounds were elucidated by spectroscopic analysis, including 2D NMR experiments. All isolates, with the exception of the isocoumarin bergenin, and identified compounds as well as antimalarial activities, are described for the first time for this species.     

A relationship between the mevalonate pathway and isoprenoid production in actinomycetes

Most Streptomyces strains are equipped with only the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the formation of isopentenyl diphosphate. In addition to this pathway, some Strepromyces strains have the mevalonate pathway to produce terpenoid antibiotics. We have previously shown that a gene cluster for biosynthesis of terpentecin, a diterpene antibiotic, was located in adjacent the mevalonate pathway gene cluster. In this study, a mevalonate pathway gene cluster was cloned from Actinoplanes sp. strain A40644, an isoprenoid antibiotic BE-40644 producer, to examine whether the mevalonate pathway genes and isoprenoid biosynthetic genes are clustered in genomic DNA. By sequencing flanking regions a probable BE-40644 biosynthetic gene cluster was found in the downstream region of the mevalonate pathway gene cluster. Heterologous expression of a 9-kb fragment confirmed that a set of the BE-40644 biosynthetic genes was involved in the fragment. This result suggested that the presence of the mevalonate pathway might be a good landmark to detect the production of isoprenoid compounds by actinomycetes.