• 【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。
  • 【长春花单萜类吲哚生物碱工程在同质和异质系统中的现状。】 复制标题 收藏 收藏
    DOI:10.1007/s10529-019-02757-4 复制DOI
    作者列表:Sharma A,Amin D,Sankaranarayanan A,Arora R,Mathur AK
    BACKGROUND & AIMS: :Catharanthus roseus synthesizes one of the most structurally, chemically and biologically active phytomolecules monoterpenoids indole alkaloids (MIAs) with having a wide range of pharmaceutical activities. Being the sole source of antineoplastic MIAs vinblastine and vincristine C. roseus has become one of the most valued plant. The low in planta availability of these MIAs and unavailability of alternative chemical synthesis system has enhanced their demand and equally let to the exorbitant market cost. To bridge this gap alternative production systems have been investigated using MIAs metabolic engineering (ME) in the homologous and heterologous systems. The availability of improved recombinant technologies along with genomics and metabolomics tools has opened the door of tremendous new potentials of ME. To encash these potentials of ME for MIAs pathway, efforts were made by expressing constitutive structure biosynthesis enzymes, transporters, and transcription factors of C. roseus MIAs biosynthesis in both homologous and heterologous systems. Here we review the knowledge of C. roseus MIAs pathway metabolic engineering in homologous and heterologous systems, gained in the past 35 years of C. roseus research.
    背景与目标: 长春花合成了一种结构,化学和生物活性最强的植物分子单萜类吲哚生物碱 (MIAs),具有广泛的药物活性。作为抗肿瘤药长春花碱和长春新碱的唯一来源,玫瑰长春新碱已成为最有价值的植物之一。这些MIAs的植物可用性低,并且无法使用替代化学合成系统,这增加了它们的需求,并同样使市场成本过高。为了弥合这一差距,已经在同源和异源系统中使用MIAs代谢工程 (ME) 研究了替代生产系统。改进的重组技术以及基因组学和代谢组学工具的可用性为ME的巨大潜力打开了大门。为了保护ME在MIAs途径中的这些潜力,我们通过在同源和异源系统中表达roseus C.MIAs生物合成的组成型结构生物合成酶,转运蛋白和转录因子做出了努力。在这里,我们回顾了在过去35年的roseus C. roseus研究中获得的在同源和异源系统中的C. roseus MIAs途径代谢工程的知识。
  • 【Pyrindemins E和F,来自海绵两栖动物的新3-烷基吡啶生物碱。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2010.11.020 复制DOI
    作者列表:Kura K,Kubota T,Fromont J,Kobayashi J
    BACKGROUND & AIMS: :Two new 3-alkylpyridine alkaloids, pyrinodemins E (1) and F (2), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1 and 2 were elucidated on the basis of spectroscopic data. Pyrinodemins E (1) and F (2) were novel 3-alkylpyridine alkaloids possessing a 4-(methoxyamino)piperidinone moiety and an indol-3-glyoxylamide moiety, respectively. Pyrinodemin E (1) showed cytotoxicity against P388 and L1210 murine leukemia cells.
    背景与目标: : 从冲绳海洋海绵两栖动物中分离出两种新的3-烷基吡啶生物碱,pyrinodemins E (1) 和F (2)。并根据光谱数据阐明了1和2的结构。吡喃基胺E (1) 和F (2) 是分别具有4-(甲氧基氨基) 哌啶酮部分和indol-3-glyoxylamide部分的新型3-烷基吡啶生物碱。吡喃基胺E (1) 显示出对P388和L1210鼠白血病细胞的细胞毒性。
  • 【生物碱在逆转人类癌症多药耐药性中的应用。】 复制标题 收藏 收藏
    DOI:10.1016/S1875-5364(18)30093-1 复制DOI
    作者列表:Wang M,Liu ZF,Tang H,Chen BA
    BACKGROUND & AIMS: :Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.
    背景与目标: : 人类癌症的多药耐药性 (MDR) 是癌症治疗的最大挑战之一。天然产物,尤其是生物碱,通过与各种靶标相互作用,对MDR具有低毒性的反向作用。在这篇综述中,我们总结了近年来主要生物碱的研究进展,包括分类,功能,机理,研究现状以及在逆转MDR中的应用。
  • 【肝毒性吡咯烷生物碱及其N-氧化物机理之间的吸收差异及其潜在的毒性影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.jep.2019.112421 复制DOI
    作者列表:Yang M,Ma J,Ruan J,Zhang C,Ye Y,Pi-Cheng Fu P,Lin G
    BACKGROUND & AIMS: ETHNOPHARMACOLOGICAL RELEVANCE:Pyrrolizidine alkaloids (PAs) are a group of phytotoxins widely present in about 3% of flowering plants. Many PA-containing herbal plants can cause liver injury. Our previous studies demonstrated that PA N-oxides are also hepatotoxic, with toxic potency much lower than the corresponding PAs, due to significant differences in their toxicokinetic fates. AIM OF STUDY:This study aimed to investigate the oral absorption of PAs and PA N-oxides for better understanding of their significant differences in toxicokinetics and toxic potency. MATERIALS AND METHODS:The oral absorption of PAs and PA N-oxides in rats and in rat in situ single pass intestine perfusion model was investigated. The intestinal permeability and absorption mechanisms of five pairs of PAs and PA N-oxides were evaluated by using Caco-2 monolayer model. RESULTS:The plasma concentrations of total PAs and PA N-oxides within 0-60 min were significantly lower in rats orally treated with a PA N-oxide-containing herbal alkaloid extract than with a PA-containing herbal alkaloid extract at the same dose, indicating that the absorption of PA N-oxides was lower than that of PAs. Using the rat in situ single pass intestine perfusion model, less cumulative amounts of retrorsine N-oxide in mesenteric blood were observed compared to that of retrorsine. In Caco-2 monolayer model, all five PAs showed absorption with Papp AtoB values [(1.43-16.26) × 10-6 cm/s] higher than those of corresponding N-oxides with Papp AtoB values lower than 1.35 × 10-6 cm/s. A further mechanistic study demonstrated that except for senecionine N-oxide, retrorsine N-oxide, and lycopsamine N-oxide, all PAs and PA N-oxides investigated were absorbed via passive diffusion. While, for these 3 PA N-oxides, in addition to passive diffusion as their primary transportation, efflux transporter-mediated active transportation was also involved but to a less extent with the efflux ratio of 2.31-3.41. Furthermore, a good correlation between lipophilicity and permeability of retronecine-type PAs and their N-oxides with absorption via passive diffusion was observed, demonstrating that PAs have a better oral absorbability than that of the corresponding PA N-oxides. CONCLUSION:We discovered that among many contributors, the lower intestinal absorption of PA N-oxides was the initiating contributor that caused differences in toxicokinetics and toxic potency between PAs and PA N-oxides.
    背景与目标:

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录