Natural antagonists of platelet-activating factor

Several groups of antagonists of platelet-activating factor (PAF) are reviewed. The characteristics of PAF binding sites on mammalian cell membranes are described together with the activities of non-specific and synthetic PAF-antagonists. The specificity of the ginkgolides to bind to PAF-receptors is discussed and the effects of these natural products in a range of biological systems is emphasized. Other groups of natural PAF-antagonists described are the lignans and gliotoxin related compounds. The structural chemistry, structure-activity relationships and pharmacological properties of these drugs are compared to the ginkgolides.     

Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents

Ginkgolides are unique twenty-carbon terpenes, occurring naturally only in the roots and leaves of Ginkgo biloba. The molecules incorporate a tert-butyl group and six 5-membered rings, and are specific and potent antagonists of platelet-activating factor (PAF), a potent inflammatory autacoid. Studies in animal models with the most potent ginkgolide, BN 52021, and other specific PAF antagonists have demonstrated that PAF plays an important role in pathologies such as asthma, shock, ischemia, anaphylaxis, graft rejection, renal disease, CNS disorders and numerous inflammatory conditions. Ginkgolides are now being developed as therapeutic agents and very promising results have been obtained in clinical trials on shock, organ preservation and thermal injury. In addition to ginkgolides, several other types of natural PAF antagonists have been identified from various medicinal plants. These compounds have not only helped to explain the pharmacological basis of several traditional medicines, but have also provided man with a valuable new class of therapeutic agents.     

Biosynthesis of unusual aminocyclitol-containing natural products

The aminocyclitol family of natural products is a class of sugar-derived microbial secondary metabolites that demonstrate significant biological activities. Within this class of natural products are the C7N-aminocyclitol-containing compounds, which were originally associated with potent sugar-hydrolase inhibition. However, recent discoveries indicate a broader array of chemical structures and biological activities of this class of compounds. Using both conventional feeding experiments and contemporary molecular genetic approaches, some progress has been made in understanding the biosynthesis of this class of natural products. Results of in silico investigation also suggest a wide distribution of this class of natural products or closely related compounds across different classes of microorganisms, including cyanobacteria and fungi. This review describes our recent progress in the biosynthetic studies of a number of C7N-aminocyclitol-containing compounds and the potential use of bioinformatic approaches to search for novel aminocyclitol-containing natural products.     

Inhibitory effects of xanthones on platelet activating factor receptor binding in vitro

Nine naturally occurring xanthones were investigated for their platelet activating factor (PAF) receptor binding inhibitory effects using rabbit platelets. 2-(3-methylbut-2-enyl)-1,3,5-trihydoxyxanthone, macluraxanthone, 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)xanthone, 6-deoxyjacareubin and 2-(3-methylbut-2-enyl)-1,3,5,6-terahydroxyxanthone showed strong inhibition with IC50 values of 4.8, 11.0, 21.0, 29.0 and 44.0 microM, respectively. The prenyl group at C-2, the dimethylprop-2-enyl group at C-4 and the hydroxyl group at C-5 are all beneficial to the binding of xanthones to the PAF receptor. The results revealed that xanthones can represent a new class of natural PAF receptor antagonists.     

新型精氨酸加压素V2受体拮抗剂的设计与生物活性研究

目的 根据药物构效关系,设计合成出一系列结构新颖的V2受体拮抗剂,以期筛选出高效低毒的此类化合物,为进行下一步的临床前研究创造条件,为新药的创制奠定基础。方法 根据“me-too”的设计思路合成一定数量结构新颖的V2受体拮抗剂。通过核磁共振氢谱(¹H-NMR)、高分辨质谱(HRMS)等手段进行结构确证,并且测定了熔点、纯度等相关理化常数。通过表达人类V2受体的细胞模型和大鼠利尿模型进行生物活性评价。结果 设计合成出12个未见文献报道的目标化合物(A1~A12),以托伐普坦为阳性对照药,其中A6,A7,A11等化合物表现出较强的生物活性,并且具有作用持续时间更长的特点。结论 化合物结构设计合理,对进一步开展V2受体拮抗剂的结构改造及其药理毒理活性研究具有一定的参考价值。     

脑卒中与血小板活化因子及其受体拮抗剂

脑卒中是一种急性脑血管疾病,具有发病率高、致残率和致死率高的特点。全球脑卒中防治形势严峻,抗血小板聚集治疗能够有效防治脑卒中。血小板活化因子(PAF)是介导血小板聚集的另一重要介质,在脑卒中病理过程中起着重要作用。近年来,PAF受体拮抗剂在脑卒中防治领域逐渐引起国际关注。该文对PAF受体拮抗剂的分类、作用机制及药物特征进行综述,以期对临床用药及新药研发提供有价值的指导和方向。     

Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding

Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.     

The 2,11-cyclized cembranoids: cladiellins, asbestinins, and briarellins (period 1998-2010)

The 2,11-cyclized cembranoids are isolated from marine invertebrates of Octocorallia species. They are a very interesting class of natural products sharing a common oxatricyclo[6.6.1.0(2,7)]pentadecane core and carrying a varied substituent pattern. This review presents their structural diversity along with the reported biological activities. The 2,11-cyclized cembranoids were comprehensively reviewed previously in 1998, and this contribution will serve as an update of that work. Since 1998 a number of structural assignments of the isolated products have been revised, some as a result of total synthesis efforts. The chemical reactivity of several of the natural compounds has been studied, and the relevance of these findings to the biosynthesis or the generation of isolation artifacts is discussed. The wide range of biological activities displayed by the 2,11-cyclized cembranoids justifies the interest shown within the synthetic chemistry community and suggests that this class of natural products remains a fruitful area for future synthetic and biological research.     

血小板活化因子及其受体拮抗剂的研究进展

目的:综述血小板活化因子(PAF)及其受体拮抗剂的研究进展。方法:根据已报道的介绍PAF及其受体拮抗剂的相关文献,介绍PAF及其拮抗剂的研究进展。结果:从PAF的结构、作用机制、PAF受体拮抗剂类型等方面介绍了PAF及其拮抗剂的研究进展。结论:PAF是具有广泛生物活性的磷脂细胞因子,参与人体多种生理、病理过程。而PAF受体拮抗剂可以拮抗PAF引起的病理反应。对PAF及其受体拮抗剂的研究对人类疾病的治疗有巨大意义。     

Inhibitory effect of compounds from Goniothalamus tapis Miq. and Goniothalamus uvaroides King on platelet-activating factor receptor binding

Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl-lactones, (-)-cryptomeridiol, liriodenine, 3-methyl-1H-benz[f]indole-4,9-dione, (-)-stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using (3) H-PAF as a ligand. Among the compounds tested, (-)-cryptomeridiol, (+)-goniothalamin and (+)-isoaltholactone exhibited a significant and concentration-dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)(50) values of 17.5, 19.7 and 46.5 μm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors.     

The genus Scutellaria an ethnopharmacological and phytochemical review

Scutellaria (HUANG QIN) (Lamiaceae), which includes about 350 species commonly known as skullcaps, is widespread in Europe, the United States and East Asia. Some species are taken to clear away the heat-evil and expel superficial evils in traditional Chinese medicine (TCM). The present paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of Scutellaria species. More than 295 compounds have been isolated, among them flavonoids and diterpenes. Studies show that Scutellaria and its active principles possess wide pharmacological actions, such as antitumor, anti-angiogenesis, hepatoprotective, antioxidant, anticonvulsant, antibacterial and antiviral activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activity from Scutellaria in vivo and in vitro. Increasing data supports application and exploitation for new drug development.     

Bioactive brominated metabolites from the Red Sea sponge Pseudoceratina arabica

Chemical investigation of the Red Sea sponge Pseudoceratina arabica has led to the isolation and identification of seven brominated compounds including two new bromotyramine derivatives, hydroxymoloka'iamine (2) and moloka'iakitamide (6), and a new brominated phenolic compound, ceratinophenol A (5), together with the known compounds moloka'iamine (1), ceratinamine (3), 5-bromo-2,3-dihydroxy-6-methoxybenzaldehyde (4), and psammaplysin-A (7). Biological evaluation of these metabolites indicated that moloka'iamine and moloka'iakitamide possess significant parasympatholytic effects on isolated rabbit heart and jejunum. This finding has important implications for further biological investigation of this class of compounds. Moreover, these compounds showed weak antibacterial and antifungal activities.     

石松生物碱化学成分和生物活性研究进展

石松生物碱是指从石松科（Lycopodiaceae）、石杉科（Huperziaceae）及其近缘亲属植物中分离得到的一类具有生源相同、结构相似且骨架丰富多样的生物碱。目前已有600余个石松生物碱被报道,其根据化学结构特征可划分为4大基本骨架类型,分别为lycopodine、lycodine、fawcettidane和miseelaneous型。miseelaneous型骨架多变,主要以phlegmarine型为主,也有少量cernuane型。部分此类化合物在胆碱酯酶抑制、神经保护和细胞毒等方面表现出良好的活性。对2015年8月—2022年1月报道的161个石松生物碱的化学结构、植物来源和生物活性进行总结,以期为该类成分的后续研究提供参考。     

Woodfordia fruticosa: traditional uses and recent findings

Woodfordia fruticosa Kurz of the family Lythraceae is a plant of tropical and subtropical region with a long history of medicinal use. A wide range of chemical compounds including tannins (especially those of macrocyclic hydrolysable class), flavonoids, anthraquinone glycosides, and polyphenols have been isolated from this species in recent times. Extracts and metabolites of this plant, particularly those from flowers and leaves, possess useful pharmacological activities. A comprehensive account of the chemical constituents and the biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance on this plant.     

益母草属萜类化学成分及其药理作用研究进展

益母草属植物中的化合物类型多样、结构丰富,其中萜类化合物是目前发现数量最多的一类,同时具有广泛的生物活性。因此,作者对益母草属萜类化合物及其药理活性进行总结归纳,为该属萜类化合物的进一步研究提供参考。     

信宜润楠的化学成分研究

通过萃取、正相硅胶、Sephadex LH-20、闪式柱色谱以及反相HPLC柱色谱等多种分离方法相结合,从信宜润楠乙醇提物中首次分离得到21个化合物;借助红外、质谱和核磁共振等波谱学分析方法鉴定了它们的结构,其中包括8个丁内酯类(1～8),8个木脂素类(9～16)和5个萜类化合物(17～21),化合物16是降七碳木脂烷类新天然产物。经体外活性筛选发现化合物5对胃癌(BGC-823)和卵巢癌(A2780)人肿瘤细胞株有选择性抑制活性,IC50分别为0.13×10-6,2.66×10-6mol.L-1;在1×10-5mol.L-1时,化合物8和9具有明显抑制PAF刺激大鼠多形核白细胞β-葡萄糖苷酸酶释放作用,抑制率分别为60.0%,54.2%。     

鞣花鞣质肠道代谢产物urolithins研究进展

鞣花鞣质是一类具有诸多生物活性的酚类化合物,近年来研究发现其发挥作用的物质基础与其肠道菌群代谢产物——尿石素密切相关。该研究就近几年国内外关于尿石素的结构特征、类型、分布,以及其改善前列腺、乳腺、结肠相关疾病,抗癌、抗氧化、抗炎等生物活性研究进行了综述,为开发和利用尿石素奠定基础。     

黄酮类化合物的药理活性研究进展

黄酮类化合物是广泛存在于自然界中的多酚类化合物,因其结构的多样性,表现出多种生物学活性。就黄酮类化合物的抗氧化、抗炎、抗诱变、抗肿瘤形成与生长等多种药理活性的研究进展进行了综述。     

海绵中活性化学成分的研究进展

海洋生物海绵的活性化学成分研究一直都是海洋药物研究的焦点。目前,从海绵中发现了大量的具有抗微生物、抗炎、抗肿瘤、抗病毒和免疫调节等活性的化学成分,其按照化学结构类型可分为脂类、大环内酯类、肽类、生物碱类、甾醇类和萜类等,并且有很多化合物已经进入临床研究。对近年来从海绵中发现的活性化学成分进行综述。     

Actinomycins with altered threonine units in the beta-peptidolactone

Five new members of the actinomycin family, actinomycins G2-G6 (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the alpha-ring of the novel compounds contains the unusual amino acid 3-hydroxy-5-methylproline, while the beta-ring includes N-methylalanine and either a chlorinated or hydroxylated threonine moiety. The chlorine-containing actinomycin G2 (2) is the main product; it exhibits strong cytotoxic and antibacterial activities. Actinomycin G5 (5) is the first actinomycin with an additional ring closure between the beta-peptidolactone and the actinoyl chromophore. Actinomycin G6 (6) resulted from the 4-hydroxythreonine-containing actinomycin G3 (3) by a 2-fold acyl shift of the beta-unit, which has not been observed before for this class of chromopeptides. The structural modification of compounds 5 and 6 goes along with an evident reduction of the biological activity. The biosynthesis of aniso-actinomycins is discussed.