• 【山豆根中喹嗪生物碱及其抗炎活性。】 复制标题 收藏 收藏
    DOI:10.1016/j.fitote.2019.104391 复制DOI
    作者列表:He LJ,Liu JS,Luo D,Zheng YR,Zhang YB,Wang GC,Li YL
    BACKGROUND & AIMS: :Two new quinolizidine-based alkaloids (2 and 12), along with ten known ones (1, 3-11) were isolated from the roots of S. tonkinensis. Their structures were determined by spectroscopic data (including NMR, MS, IR, and UV), X-ray single crystal diffraction, electronic circular dichroism analyses (ECD), and comparing with related literatures. Compounds 1, 3-12 at non-toxic concentrations exhibited potent anti-inflammatory activities according to in vitro and in vivo anti-inflammatory tests. Among them, (-)-anagyrine (4), sophocarpine (8), 14β-hydroxymatrine (10), and 7β-sophoramine (12) showed more potent in vitro anti-inflammatory activities, and 5α,14β-dihydroxymatrine (2), (-)-anagyrine (4), sophocarpine (8), and 5α-hydroxymatrine (9) exhibited better in vivo anti-inflammatory effects.
    背景与目标: : 从tonkinensis的根中分离出两种新的基于喹啉嗪的生物碱 (2和12) 以及十种已知的生物碱 (1,3-11)。通过光谱数据 (包括NMR,MS,IR和UV),x射线单晶衍射,电子圆二色性分析 (ECD) 确定了它们的结构,并与相关文献进行了比较。根据体外和体内抗炎试验,无毒浓度的化合物1、3-12表现出有效的抗炎活性。其中,(-)-anagyrine (4),槐果碱 (8),14β-羟基苦参碱 (10) 和7β-槐胺 (12) 表现出更有效的体外抗炎活性,而5α,14β-二羟基苦参碱 (2),(-)-anagyrine (4),槐果碱 (8) 和5α-羟基苦参碱 (9) 表现出更好的体内抗炎作用。
  • 【具有潜在抗癌活性的吲哚生物碱。】 复制标题 收藏 收藏
    DOI:10.2174/1568026620666200622150325 复制DOI
    作者列表:Xu D,Xu Z
    BACKGROUND & AIMS: :Indole alkaloids, which are abundant in nature, are a significant source of pharmacologically active compounds. Indole alkaloids have the potential to exert anticancer activity via various antiproliferative mechanisms, and some of them, such as Vinblastine and Vincristinem, have already used in clinics or under clinical evaluations for the treatment of cancers. Therefore, indole alkaloids occupy an important position in the discovery of novel anticancer agents. This review emphasizes the recent development of indole alkaloids as potential anticancer agents, their structure-activity relationship, and mechanisms of action covering the articles published from 2015 to 2020.
    背景与目标: : 吲哚生物碱在自然界中含量丰富,是药理活性化合物的重要来源。吲哚生物碱具有通过各种抗增殖机制发挥抗癌活性的潜力,其中一些 (例如长春碱和长春碱) 已在临床或临床评估中用于治疗癌症。因此,吲哚生物碱在新型抗癌药物的发现中占有重要地位。这篇综述强调了吲哚生物碱作为潜在抗癌剂的最新发展,它们的构效关系以及涵盖2020年2015年发表的文章的作用机理。
  • 【煮熟的羽扇豆及其纯化的生物碱对2型糖尿病患者的降血糖作用。】 复制标题 收藏 收藏
    DOI:10.3305/nh.2012.27.4.5761 复制DOI
    作者列表:Baldeón ME,Castro J,Villacrés E,Narváez L,Fornasini M
    BACKGROUND & AIMS: :Developing countries are experiencing an epidemic of chronic non-communicable chronic diseases with high socio-economic costs. Studies of traditional foods with beneficial health properties could contribute to diminish these problems. Legumes rich in proteins like Lupinus mutabilis decreases blood glucose and improves insulin sensitivity in animals and humans. We report the results of a phase II clinical trial conducted to assess the role of cooked L. mutabilis and its purified alkaloids on blood glucose and insulin in volunteers with diabetes. Results indicate that consumption of cooked L. mutabilis or its purified alkaloids decreased blood glucose and insulin levels. The decreases in serum glucose concentrations from base line to 90 minutes were statistically significant within both treatment groups; however, there were not differences between groups. Serum insulin levels were also decreased in both groups however the differences were not statistically significant. None of the volunteers in either group presented side effects.
    背景与目标: : 发展中国家正在经历一场社会经济代价高昂的慢性非传染性慢性病流行。对具有有益健康特性的传统食品的研究可能有助于减少这些问题。富含蛋白质的豆类植物,如羽扇豆,可降低动物和人类的血糖并改善胰岛素敏感性。我们报告了一项II期临床试验的结果,该试验旨在评估煮熟的L. mutabilis及其纯化的生物碱对糖尿病志愿者的血糖和胰岛素的作用。结果表明,食用煮熟的L. mutabilis或其纯化的生物碱可降低血糖和胰岛素水平。在两个治疗组中,从基线到90分钟的血清葡萄糖浓度降低在统计学上是显着的; 但是,两组之间没有差异。两组的血清胰岛素水平也均降低,但差异无统计学意义。两组的志愿者均未出现副作用。
  • 【球孢白僵菌中2-吡啶酮生物碱和四氧嗪的隔离与鉴定。】 复制标题 收藏 收藏
    DOI:10.1080/14786419.2016.1269091 复制DOI
    作者列表:Andrioli WJ,Lopes AA,Cavalcanti BC,Pessoa C,Nanayakkara NPD,Bastos JK
    BACKGROUND & AIMS: :Two novel compounds bearing heterocyclic nitrogen, 2-pyridone alkaloid (1) and alloxazine derivative (2), along with the known pretenellin B (3), pyridovericin (4) and lumichrome (5) were isolated from a culture of the entomopathogenic fungal strain Beauveria bassiana. The chemical structures of 2-pyridone alkaloid and alloxazine derivative were established on the basis of the interpretation of spectroscopic data. The isolated compounds were evaluated in a panel of five cancer cell lines and pyridovericin exhibited cytotoxicity (IC50, μM) against cancer cell lines: HL-60 (25.9 ± 0.3), HCT8 (34.6 ± 3.6), MDA-MB435 (34.8 ± 3.8) and SF295 (31.1 ± 0.6). Considering that other pyridone compounds display good cytotoxic activity, it would be suggested to obtain new semi synthetic derivatives of pyridovericin, for the development of new cytotoxic chemical entities.
    背景与目标: : 从培养物中分离出两种带有杂环氮的新型化合物,2-吡啶酮生物碱 (1) 和alloxazine衍生物 (2) 以及已知的pretenellin B (3),pyridovericin (4) 和lumichrome (5)。昆虫病原真菌菌株球孢白僵菌。在光谱数据解释的基础上,建立了2-吡啶酮生物碱和alloxazine衍生物的化学结构。在一组5种癌细胞系中评估分离的化合物,并且吡啶并对癌细胞系表现出细胞毒性 (IC50,μ m): HL-60 (25.9 ± 0.3),HCT8 (34.6 ± 3.6),MDA-MB435 (34.8 ± 3.8) 和SF295 (31.1 ± 0.6)。考虑到其他吡啶酮化合物显示出良好的细胞毒性活性,建议获得新的吡啶酮半合成衍生物,以开发新的细胞毒性化学实体。
  • 【Β-carboline生物碱harmine和harmaline在体外人体细胞测定中的细胞毒性。】 复制标题 收藏 收藏
    DOI:10.1016/j.etp.2007.12.003 复制DOI
    作者列表:Jiménez J,Riverón-Negrete L,Abdullaev F,Espinosa-Aguirre J,Rodríguez-Arnaiz R
    BACKGROUND & AIMS: :beta-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into DNA. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro are not found in the literature. In the present study the toxicities of one full aromatic beta-carboline alkaloid (harmine) and one dihydro-beta-carboline alkaloid (harmaline) were evaluated by means of two in vitro human cell assays: the cytochalasin-B blocked micronucleus (CBMN) assay and the viability/colony formation assay with four different human cultured non-transformed (CCD18Lu) and transformed (HeLa, C33A and SW480) cells. Neither alkaloid was able to induce micronuclei levels above that of control levels in a wide range of doses tested; although, harmine at the highest concentrations assayed induced apoptotic as well as necrotic cells. Harmine produced a good viability of all cell lines assayed (control and tumor) while harmaline significantly reduced the viability of transformed and non-transformed cell lines in a dose-dependent manner. Harmine displayed a dose-dependent inhibitory effect on cell proliferation against all human carcinoma cells, but the SW480 transformed cell line showed a higher sensitivity. These results suggested that harmine was identified as a useful inhibitor of tumor development.
    背景与目标: : β-Carboline生物碱是天然产物,广泛分布于植物中,也存在于酒精饮料,煮熟的食物和烟草烟雾中。各种作者报道了原核和真核细胞中几种carboline的遗传毒性活性,这归因于它们插入DNA的能力。但是在文献中未发现有关体外人类细胞的遗传毒性和细胞毒性能力的研究。在本研究中,通过两种体外人类细胞测定法评估了一种全芳香族 β-碳环碱生物碱 (harmine) 和一种二氢-β-碳环碱生物碱 (harmaline) 的毒性: 细胞松弛素-B用四种不同的人类培养的未转化 (CCD18Lu) 和转化 (HeLa,C33A和SW480) 细胞阻断微核 (CBMN) 测定和活力/集落形成测定。在广泛的测试剂量范围内,这两种生物碱都无法诱导高于对照水平的微核水平; 尽管,在最高浓度下测定的harmine诱导了凋亡和坏死细胞。Harmine产生了所有测定的细胞系 (对照和肿瘤) 的良好活力,而harmaline以剂量依赖性方式显着降低了转化和非转化细胞系的活力。Harmine对所有人类癌细胞的细胞增殖均表现出剂量依赖性抑制作用,但SW480转化的细胞系显示出更高的敏感性。这些结果表明,harmine被确定为肿瘤发展的有用抑制剂。
  • 【来自黄连的单萜类吲哚生物碱及其细胞毒性。】 复制标题 收藏 收藏
    DOI:10.1080/10286020.2017.1313242 复制DOI
    作者列表:Yan TL,Han DX,Hu J,Huang XY,Wang HK
    BACKGROUND & AIMS: :Phytochemical investigation on the 70% ethanol extract of the leaves of Alstonia mairei resulted in the isolation of three new monoterpenoid indole alkaloids, alstomairines A-C (1-3), along with one known compound, alpneumine A (4). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D and 2D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against four osteosarcoma cell lines. Consequently, alkaloids 2 and 3 exhibited cytotoxic activities for all tested tumor cell lines with IC50 values from 9.2 to 13.0 μM.
    背景与目标: : 对Alstonia mairei叶片的70% 乙醇提取物的植物化学研究导致隔离出三种新的单萜类吲哚生物碱alstomaines a-c (1-3) 以及一种已知化合物alpneumines A (4)。所有化合物的结构阐明均通过光谱方法 (例如1D和2D NMR,IR,UV和hresms) 完成。在体外测试了分离出的化合物对四种骨肉瘤细胞系的细胞毒性活性。因此,生物碱2和3对所有测试的肿瘤细胞系表现出细胞毒性活性,IC50值为9.2至13.0微米。
  • 【黄连二萜生物碱的血液刺激作用机制。】 复制标题 收藏 收藏
    DOI:10.1007/s10517-013-2151-z 复制DOI
    作者列表:Zyuz'kov GN,Zhdanov VV,Miroshnichenko LA,Udut EV,Simanina EV,Stavrova LA,Agafonov VI,Chaikovskiy AV,Minakova MY,Povet'eva TN,Suslov NI,Krapivin AV,Nesterova YV,Semenov AA,Reykhart DV,Dygai AM
    BACKGROUND & AIMS: :A mixture of diterpene alkaloids of Aconitum baicalense exhibited pronounced regenerative hemostimulating properties on the model of cytostatic myelosuppression. The therapeutic effect is based on activation of hemopoietic progenitor cells against the background of increased feeder capacity of stromal compartment of the hemopoiesis-inducing microenvironment and decreased count of mesenchymal stem cells in the bone marrow.
    背景与目标: : 在细胞抑制性骨髓抑制模型上,黄头乌头的二萜生物碱混合物表现出明显的再生血液刺激特性。治疗效果是基于造血祖细胞的激活,而造血诱导微环境的基质区室饲养能力增加,骨髓中间充质干细胞计数减少。
  • 【麦角生物碱。6-甲基-8-麦角烯作为催乳素释放抑制剂的合成。】 复制标题 收藏 收藏
    DOI:10.1021/jm00243a006 复制DOI
    作者列表:Li GS,Robinson JM,Floss HG,Cassady JM
    BACKGROUND & AIMS: :A general synthetic route from elymoclavine (4a) to a variety of C-17 substituted 8-ergolenes has been established. [The C-17 position is the carbon attached to C-8 of the ergoline (1) skeleton as indicated in structure 2.] This route involves displacement reactions on the allylic chloride (4h) prepared from 4a by reaction with thionyl chloride. Conversion of the naturally occurring tricyclic clavines, chanoclavine I (5a) and isochanoclavine I (5b), to the tetracyclic clavine, agroclavine (4i), has been achieved. The new compounds prepared were tested for prolactin-inhibiting ability and were found to possess activity. One of the compounds prepared, 6-methyl-8-ergolenylacetamide (4k), was very potent, comparing favorably in activity to the best prolactin inhibitors reported to date.
    背景与目标: : 已经建立了从elymoclavine (4a) 到多种C-17取代的8-麦角烯的一般合成路线。[C-17位置是附着在麦角灵 (1) 骨架的C-8上的碳,如结构2所示。]该路线涉及通过与亚硫酰氯反应在4a制备的烯丙基氯 (4h) 上的置换反应。已经实现了将天然存在的三环锁骨蛋白 (chanoclavine I (5a) 和isochanoclavine I (5b)) 转化为四环锁骨蛋白 (agroclavine (4i))。测试了制备的新化合物的催乳素抑制能力,并发现其具有活性。制备的化合物之一,6-甲基-8-麦角烯基乙酰胺 (4k) 非常有效,与迄今为止报道的最佳催乳素抑制剂相比,活性具有优势。
  • 【烟草生物碱的生物合成需要PIP家族蛋白。】 复制标题 收藏 收藏
    DOI:10.1007/s11103-008-9424-3 复制DOI
    作者列表:Kajikawa M,Hirai N,Hashimoto T
    BACKGROUND & AIMS: :Plants in the Nicotiana genus produce nicotine and related pyridine alkaloids as a part of their chemical defense against insect herbivores. These alkaloids are formed by condensation of a derivative of nicotinic acid, but the enzyme(s) involved in the final condensation step remains elusive. In Nicotiana tabacum, an orphan reductase A622 and its close homolog A622L are coordinately expressed in the root, upregulated by methyl jasmonate treatment, and controlled by the NIC regulatory loci specific to the biosynthesis of tobacco alkaloids. Conditional suppression of A622 and A622L by RNA interference inhibited cell growth, severely decreased the formation of all tobacco alkaloids, and concomitantly induced an accumulation of nicotinic acid beta-N-glucoside, a probable detoxification metabolite of nicotinic acid, in both hairy roots and methyl jasmonate-elicited cultured cells of tobacco. N-methylpyrrolinium cation, a precursor of the pyrrolidine moiety of nicotine, also accumulated in the A622(L)-knockdown hairy roots. We propose that the tobacco A622-like reductases of the PIP family are involved in either the formation of a nicotinic acid-derived precursor or the final condensation reaction of tobacco alkaloids.
    背景与目标: : 烟草属植物产生尼古丁和相关的吡啶生物碱,作为其对昆虫食草动物的化学防御的一部分。这些生物碱是由烟酸衍生物的缩合形成的,但是最终缩合步骤中涉及的酶仍然难以捉摸。在烟草中,孤儿还原酶A622及其紧密同源物A622L在根部协同表达,通过茉莉酸甲酯处理上调,并受烟草生物碱生物合成特异性的NIC调节基因座控制。RNA干扰对A622和A622L的条件抑制抑制了细胞的生长,严重减少了所有烟草生物碱的形成,并同时诱导了烟酸 β-N-葡萄糖苷的积累,烟酸 β-N-葡萄糖苷是烟酸的可能解毒代谢产物,在毛状根和茉莉酸甲酯诱导的烟草培养细胞中。N-甲基吡咯烷阳离子,尼古丁的吡咯烷部分的前体,也积累在A622(L)-敲低的毛状根中。我们建议PIP家族的烟草A622-like还原酶参与烟酸衍生前体的形成或烟草生物碱的最终缩合反应。
  • 【5 ',6'-脱氢guiachrysine和5 ',6'-脱氢guiaflavine,两种来自马钱子茎皮的四元吲哚生物碱。】 复制标题 收藏 收藏
    DOI:10.1016/s0031-9422(01)00255-2 复制DOI
    作者列表:Penelle J,Christen P,Molgó J,Tits M,Brandt V,Frédérich M,Angenot L
    BACKGROUND & AIMS: Two new quaternary indole alkaloids 5',6'-dehydroguiachrysine (1) and 5',6'-dehydroguiaflavine (2) were isolated from Strychnos guianensis stem bark. Their structures were determined by analysis of spectral data. Their inhibitory effects on neuromuscular transmission are also reported and compared to that of other quaternary alkaloids.

    背景与目标: 从马钱子茎皮中分离出两种新的季吲哚生物碱5 ',6'-脱氢桂花碱 (1) 和5 ',6'-脱氢桂花碱 (2)。通过分析光谱数据确定它们的结构。还报道了它们对神经肌肉传递的抑制作用,并与其他第四纪生物碱进行了比较。
  • 【在确定的培养基中,草内生菌Neotyphodium uncinatum生产loline生物碱。】 复制标题 收藏 收藏
    DOI:10.1016/s0031-9422(01)00272-2 复制DOI
    作者列表:Blankenship JD,Spiering MJ,Wilkinson HH,Fannin FF,Bush LP,Schardl CL
    BACKGROUND & AIMS: Lolines (saturated 1-aminopyrrolizidines with an oxygen bridge) are insecticidal alkaloids produced in symbioses of certain Epichloë (anamorph-Neotyphodium) species (fungal endophytes) with grasses, particularly of the genera Lolium and Festuca. Prior to the present study, it was unknown whether lolines were of plant or fungal origin. Neotyphodium uncinatum, the common endophyte of meadow fescue (Lolium pratense=Festuca pratensis) produced loline, N-acetylnorloline, and N-formylloline when grown in the defined minimal media at pH 5.0-7.5, with both organic and inorganic nitrogen sources and sugars as carbon sources. In contrast, lolines were not detected in complex medium cultures. GC-MS and 13C NMR spectroscopic analyses confirmed the identity of the alkaloids isolated from the defined medium cultures. Lolines accumulated to ca. 700 mg/l (4 mM) in cultures with 16.7 mM sucrose and 15-30 mM asparagine, ornithine or urea. Kinetics of loline production and fungal growth were assessed in defined medium with 16.7 mM sucrose and 30 mM ornithine. The alkaloid production rate peaked after the onset of stationary phase, as is common for secondary metabolism in other microbes.

    背景与目标: Lolines (具有氧桥的饱和1-氨基吡咯烷类) 是在某些epichlo ë (anamorph-Neotyphodium) 物种 (真菌内生菌) 与草,特别是Lolium和Festuca属的共生生物中产生的杀虫生物碱。在本研究之前,尚不清楚lolines是植物还是真菌来源。草甸羊茅 (Lolium pratense = Festuca pratensis) 的常见内生菌uncinatum Neotyphodium uncinatum当在pH 5.0-7.5的规定的最小培养基中生长时,会产生loline,N-乙酰去甲loline和N-forlylloline,有机和无机氮源和糖作为碳源。相反,在复杂的培养基中未检测到lolines。Gc-ms和13C NMR光谱分析证实了从确定的培养基中分离出的生物碱的身份。在具有16.7 mM蔗糖和15-30 mM天冬酰胺、鸟氨酸或尿素的培养物中,Lolines积累至约700 mg/l (4毫米)。在具有16.7 mM蔗糖和30 mM鸟氨酸的限定培养基中评估了loline产生和真菌生长的动力学。生物碱的产生速率在固定相开始后达到峰值,这在其他微生物的次生代谢中很常见。
  • 【延胡索体细胞胚衍生植物块茎形成原小檗碱型生物碱。】 复制标题 收藏 收藏
    DOI:10.1055/s-2001-18853 复制DOI
    作者列表:Lee YL,Sagare AP,Lee CY,Feng HT,Ko YC,Shaw JF,Tsay HS
    BACKGROUND & AIMS: The effects of 0.5 - 5 mg/l abscisic acid [ABA], 0.5 - 10 mg/l (2RS,3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-ol [paclobutrazol] and 0.5 - 2 mg/l alpha-cyclopropyl-alpha-(4-methoxyphenyl)-5-pyrimidinemethanol [ancymidol], 0.5 - 5 mg/l gibberellic acid [GA(3)] and 15 - 100 mg/l polyethylene glycol [PEG] 4000 supplemented in half-strength Murashige and Skoog's (MS) medium on the production of the two major protoberberine-type alkaloids (D,L-tetrahydropalmatine and D-corydaline) by the tubers of somatic embryo-derived plants of Corydalis yanhusuo were examined. Somatic embryo derived plants were also maintained for 6 months on half-strength MS medium containing 0.1 mg/l GA(3) or 0.5 mg/l paclobutrazol. The alkaloid contents were determined by high performance liquid chromatography (HPLC). The analysis revealed that the contents of D,L-tetrahydropalmatine and D-corydaline in the tubers of somatic embryo-derived plants were higher than the marketed crude drug and varied with growth regulator/PEG-4000 treatment and the age of the plant.

    背景与目标: 0.5 - 5 mg/l脱落酸 [ABA],0.5-10 mg/l (2RS,3RS)-1-(4-氯苯基)-4,4-二甲基-2-(1,2,4-三唑-1-基) pentan-3-ol [多效唑] 和0.5-2 mg/l α-环丙基-α-(4-甲氧基苯基)-5-嘧啶乙醇 [ancymidol],0.5-5 mg/l赤霉素 [GA(3)] 和15-100 mg/l聚乙二醇 [PEG] 4000在半强度Murashige和Skoog's (MS) 培养基中补充生产两种主要的原小檗碱型生物碱 (D,检查了延胡索体细胞胚衍生植物块茎的L-四氢巴马汀和D-延胡索。体细胞胚衍生植物也在含有0.1 mg/l GA(3) 或0.5 mg/l多效唑的半强度MS培养基上保持6个月。确定了生物碱含量通过高效液相色谱 (HPLC)。分析表明,D,体细胞胚衍生植物块茎中的L-四氢巴马汀和D-延胡索碱高于市售粗药,并且随生长调节剂/PEG 4000处理和植物年龄而变化。
  • 【石蒜生物碱及其对星形细胞瘤和神经胶质瘤细胞系的特殊细胞毒性。】 复制标题 收藏 收藏
    DOI:10.1007/s12272-013-0089-3 复制DOI
    作者列表:Cao P,Pan DS,Han S,Yu CY,Zhao QJ,Song Y,Liang Y
    BACKGROUND & AIMS: :Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and (+)-3-hydroxy-anhydrolycorine N-oxide (4). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (¹H-¹H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3). Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC₅₀ of 9.2-11.3 μM and 10.4-12.2 μM respectively.
    背景与目标: : 石蒜鳞茎的乙醇提取物的植物化学研究提供了四种新的生物碱,()-N-甲氧基羰基-nandigerine (1),()-N-甲氧基羰基-lindcarpine (2),()-10-o-甲基hernovine N-氧化物 (3),和 (+)-3-羟基-水解蛋白N-氧化物 (4)。除高分辨率质谱外,所有化合物的结构阐明均通过光谱方法进行,例如1D和2D (¹ h-¹ h cocy,HMQC和HMBC) NMR光谱。在体外评估了所有生物碱对八种肿瘤细胞系 (BEN-MEN-1,CCF-STTG1,CHG-5,SHG-44,U251,BGC-823,HepG2和SK-OV-3) 的细胞毒性活性。生物碱1和2对星形细胞瘤和神经胶质瘤细胞系表现出特殊的细胞毒性活性,其ic分别为9.2-11.3微米和10.4-12.2微米。
  • 【在一项为期28天的喂养研究中,肝毒性吡咯烷生物碱在大鼠肝脏中诱导DNA损伤反应。】 复制标题 收藏 收藏
    DOI:10.1007/s00204-020-02779-2 复制DOI
    作者列表:Ebmeyer J,Rasinger JD,Hengstler JG,Schaudien D,Creutzenberg O,Lampen A,Braeuning A,Hessel-Pras S
    BACKGROUND & AIMS: :Pyrrolizidine alkaloids (PA) are secondary plant metabolites that occur as food and feed contaminants. Acute and subacute PA poisoning can lead to severe liver damage in humans and animals, comprising liver pain, hepatomegaly and the development of ascites due to occlusion of the hepatic sinusoids (veno-occlusive disease). Chronic exposure to low levels of PA can induce liver cirrhosis and liver cancer. However, it is not well understood which transcriptional changes are induced by PA and whether all hepatotoxic PA, regardless of their structure, induce similar responses. Therefore, a 28-day subacute rat feeding study was performed with six structurally different PA heliotrine, echimidine, lasiocarpine, senecionine, senkirkine, and platyphylline, administered at not acutely toxic doses from 0.1 to 3.3 mg/kg body weight. This dose range is relevant for humans, since consumption of contaminated tea may result in doses of ~ 8 µg/kg in adults and cases of PA ingestion by contaminated food was reported for infants with doses up to 3 mg/kg body weight. ALT and AST were not increased in all treatment groups. Whole-genome microarray analyses revealed pronounced effects on gene expression in the high-dose treatment groups resulting in a set of 36 commonly regulated genes. However, platyphylline, the only 1,2-saturated and, therefore, presumably non-hepatotoxic PA, did not induce significant expression changes. Biological functions identified to be affected by high-dose treatments (3.3 mg/kg body weight) comprise cell-cycle regulation associated with DNA damage response. These functions were found to be affected by all analyzed 1,2-unsaturated PA.In conclusion, 1,2-unsaturated hepatotoxic PA induced cell cycle regulation processes associated with DNA damage response. Similar effects were observed for all hepatotoxic PA. Effects were observed in a dose range inducing no histopathological alterations and no increase in liver enzymes. Therefore, transcriptomics studies identified changes in expression of genes known to be involved in response to genotoxic compounds at PA doses relevant to humans under worst case exposure scenarios.
    背景与目标: : 吡咯烷生物碱 (PA) 是作为食物和饲料污染物出现的次生植物代谢产物。急性和亚急性PA中毒可导致人和动物的严重肝损害,包括肝痛,肝肿大和由于肝窦闭塞 (静脉闭塞性疾病) 而导致腹水的发展。长期暴露于低水平的PA可诱发肝硬化和肝癌。然而,尚不清楚PA诱导的转录变化以及是否所有肝毒性PA (无论其结构如何) 诱导相似的反应。因此,进行了28天的亚急性大鼠喂养研究,使用六种结构不同的PA日光三碱,echimidine,lasiocarpine,senecionine,senkirkine和platyphylline,以0.1至3.3 mg/kg体重的非急性毒性剂量给药。该剂量范围与人类有关,因为食用受污染的茶可能导致成人的剂量为   〜   8 µ g/kg,据报道,婴儿的剂量不超过3 mg/kg体重,被受污染的食物摄入PA。所有治疗组的ALT和AST均未升高。全基因组微阵列分析显示,高剂量治疗组对基因表达有明显影响,从而产生了一组36个常用调控基因。然而,仅有的1,2-饱和的鸭嘴碱,因此可能是非肝毒性的PA,没有引起明显的表达变化。被鉴定为受大剂量治疗 (3.3 mg/kg体重) 影响的生物学功能包括与DNA损伤反应相关的细胞周期调节。发现这些功能受所有分析的1,2-不饱和PA的影响。总之,1,2-不饱和肝毒性PA诱导了与DNA损伤反应相关的细胞周期调节过程。在所有肝毒性PA中观察到类似的效果。在剂量范围内观察到效果,未引起组织病理学改变,肝酶也未增加。因此,转录组学研究确定了在最坏情况下暴露于与人类相关的PA剂量下,已知与遗传毒性化合物反应有关的基因表达的变化。
  • 【将生物活性阿波啡生物碱重新用作外排泵抑制剂。】 复制标题 收藏 收藏
    DOI:10.1016/j.fitote.2019.104371 复制DOI
    作者列表:Avci FG,Atas B,Aksoy CS,Kurpejovic E,Gulsoy Toplan G,Gurer C,Guillerminet M,Orelle C,Jault JM,Sariyar Akbulut B
    BACKGROUND & AIMS: :Extrusion of drugs or drug-like compounds through bacterial efflux pumps is a serious health issue that leads to loss in drug efficacy. Combinatorial therapies of low-efficacy drugs with efflux pump inhibitors may help to restore the activities of such drugs. In this quest, natural products are attractive molecules, since in addition to their wide range of bioactivities they may inhibit efflux pumps. The current work repurposed the bioactive alkaloid roemerine as a potential efflux pump inhibitor. In Bacillus subtilis, both Bmr and BmrA, belonging to the major facilitator and the ATP-binding cassette superfamilies, respectively, were found to be inhibited by roemerine. Scanning electron microscopy and RNA-Seq analyses showed that it potentiated the effect of berberine. Growth rates and checkerboard assays confirmed the synergy of roemerine and berberine and that roemerine prevented berberine efflux by inhibiting Bmr. Transport assays with inverted membrane vesicles prepared from Escherichia coli overexpressing BmrA showed that increasing roemerine concentration decreased the transport of doxorubicin, the BmrA substrate, confirming that roemerine may also be considered as an inhibitor of BmrA. Thus, these findings suggest that conjugation of roemerine to substrates of efflux pumps, Bmr and BmrA, may help to potentiate the activity of their drug substrates.
    背景与目标: : 通过细菌外排泵挤出药物或类药物化合物是一个严重的健康问题,导致药物功效下降。低效药物与外排泵抑制剂的组合疗法可能有助于恢复此类药物的活性。在这一探索中,天然产物是有吸引力的分子,因为除了它们广泛的生物活性外,它们还可能抑制外排泵。当前的工作将生物活性生物碱roemerine重新用作潜在的外排泵抑制剂。在枯草芽孢杆菌中,发现分别属于主要促进剂和ATP结合盒超家族的Bmr和BmrA均被roemerine抑制。扫描电子显微镜和RNA-Seq分析表明,它增强了小檗碱的作用。生长速率和棋盘分析证实了罗梅林和小檗碱的协同作用,并且罗梅林通过抑制Bmr来防止小檗碱的外排。用过表达BmrA的大肠杆菌制备的倒置膜囊泡进行的运输分析表明,增加的roemerine浓度会降低BmrA底物阿霉素的运输,这证实了roemerine也可以被认为是BmrA的抑制剂。因此,这些发现表明,将roemerine与外排泵Bmr和BmrA的底物结合可能有助于增强其药物底物的活性。

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