Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro

A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism. From the results obtained from the radioligand-binding assay of the pure compounds, including the commercially available protopine (6), it was evident that the activity on the 5-HT(1A) receptor was at least partly due to the presence of the aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155 nM and a K(i) of 85 nM.     

Commercial valerian interactions with [3H]Flunitrazepam and [3H]MK-801 binding to rat synaptic membranes

Valeriana officinalis extracts are used in folkloric medicine for their sedative, hypnotic and tranquilizer effects. Using [3H]flunitrazepam binding as an indicator, the interactions of commercial Valerian extracts with GABA(A) receptors were examined. There was considerable fluctuation among the different extracts, some mildly enhanced [3H]flunitrazepam binding, others had no effect and others had inhibitory effects, independent of standardization by valerenic acid. Central depression can also be accomplished by a reduction of excitatory transmission. Valerian extracts had modest inhibitory effects on [3H]MK-801 binding, an indicator of NMDA-Valerian interactions. Spectral analyses (UV region) did not show marked differences among the different extracts. The inhibitory effects of one of the extracts on [3H]flunitrazepam binding was somewhat stable, while on [3H]MK-801 binding the inhibitory effects were lost within months. These results suggest that particular care should be taken in analysing and interpreting results from commercial Valerian preparations.     

Inhibition of gastric H+,K+-ATPase activity by flavonoids, coumarins and xanthones isolated from Mexican medicinal plants

Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency. The xanthones inhibited the H+,K+-ATPase with IC50 values ranging from 47 microM to 1.6 mM. Coumarins inhibited H+,K+-ATPase with IC50 values of 110 and 638 microM. IC50 values for the flavonoids ranged from 9.6 to 510 microM among which minimiflorin was the most potent. The results suggest that H+,K+-ATPase is sensitive to inhibition by several types of structurally different natural compounds. The potency of the effects on gastric H+,K+-ATPase depends on the presence, position and number of hydroxyls groups in the molecule. Collectively, these results suggest a potential for important pharmacological and toxicological interactions by these types of natural products at the level of H+,K+-ATPase which may explain, at least in part, the gastroprotective properties, indicated by traditional medicine, of the plants from which these compounds were isolated.     

Prevention of oxidative injury by flavonoids from stems and leaves of Scutellaria baicalensis Georgi in PC12 cells

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effects of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (SSF) against hydrogen peroxide (H2O2)-induced rat pheochromocytoma line PC12 injury were evaluated by cell lesion, free radicals and ATPase disorders. Following a 30 min exposure of the cells to H2O2 (100 microm), a marked decrease in cell survival and activity of superoxide dismutase (SOD) and Na+-K+-ATPase as well as an increase of malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. Pretreatment of the cells with SSF (18-76 microg/mL) prior to H2O2 exposure notably elevated the cell survival and activity of SOD and Na+-K+-ATPase, and lowered the MDA level and LDH release. Neuroprotection by SSF was also observed in animal models. The present results indicated that SSF exerts neuroprotective effects against H2O2 toxicity, which might be of importance and might contribute to its clinical efficacy for the treatment of neurodegenerative disease.     

Synthesis of [4,5-3H]-Exo-3,6-epoxyhexahydrophthatic anhydride

A convenient two-step synthesis of [4,5-³H]-Exo-3,6-epoxyhexahydrophthatic anhydride ((4,5-³H)-norcantharidin) consists of furan reacting with maleic anhydride to form dehydronorcantharidin. Then addition of tritium to dehydronorcantharidin with catalyst to form [4,5-³H]-norcantharidin. The specific activity and radiochemical purity were 56 Ci/mmol and 98%, respectively.     

Effects of linalool on [(3)H]MK801 and [(3)H] muscimol binding in mouse cortical membranes

Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool-producing species are used in traditional medical systems for sedative purposes, including the interruption and prevention of seizures. Previous studies in mice revealed that linalool modulates glutamatergic (competitive antagonism of L-[(3)H]glutamate binding, delayed intraperitoneal NMDA-induced convulsions and blockade of intracerebroventricular Quin-induced convulsions) and GABAergic transmission (protection against pentylenetetrazol and picrotoxin-induced convulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [(3)H]MK801 (NMDA antagonist) and [(3)H]muscimol (GABA(A) agonist) to mouse cortical membranes. Linalool showed a dose dependent non-competitive inhibition of [(3)H]MK801 binding (IC(50) = 2.97 mM) but no effect on [(3)H]muscimol binding. The data suggest that the anticonvulsant mode of action of linalool includes a direct interaction with the NMDA receptor complex. The data do not, however, support a direct interaction of linalool with GABA(A) receptors, although changes in GABA-mediated neuronal inhibition or effects on GABA release and uptake cannot be ruled out.     

Synthesis of [3,5-14C]trachelanthamidine and [5-3H]isoretronecanol and their incorporation into the retronecine moiety of riddelliine in Senecio riddellii

(+/-)-[3,5-14C]Trachelanthamidine and (+/-)-[5-3H]isoretronecanol, which are diastereomers, were prepared from potassium [14C]cyanide and [5-3H]proline, respectively. These compounds and [1,4-14C]putrescine were administered to Senecio riddellii plants resulting in the formation of labeled riddelliine, in which almost all the radioactivity was located in its retronecine moiety. The activity of the beta-alanine obtained by degradation of the retronecine was consistent with specific labeling of this pyrrolizidine base at the expected positions. The extremely high absolute incorporation (15.1, 22.1%) of trachelanthamidine into riddelliine strongly favors this 1-hydroxymethylpyrrolizidine as the one on the main biosynthetic pathway to retronecine. The lower incorporation (0.75%) of isoretronecanol may represent a minor or aberrant pathway to retronecine.     

Inhibition of angiotensin II receptor binding by quinolone alkaloids from Evodia rutaecarpa

A biologically monitored fractionation of methanol extracts of the fruit of Evodia rutaecarpa led to the isolation of quinolone alkaloids, evocarpin (1), 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone (2) and 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone (3) as blockers of angiotensin II receptor binding with IC₅₀ values of 43.4 μM, 34.1 μM and 48.2 μM, respectively. © 1998 John Wiley & Sons, Ltd.     

Cationic reduction of bastadin-4 to bastadin-5. Preparation of 5-[2h]-bastadin-5 by site-specific isotopic labeling

A chemoselective conversion of bastadin-4 to the important Ca2+ channel modulator bastadin-5 (1a) has been achieved using cationic hydrogenation (Et3SiH, TFA, 60%). Specifically deuterated bastadin-5 (1b, >95 at. %) was prepared following this method and the simplified 1H NMR H-5/H2-6 spin system of 1b exploited to study temperature-dependent macrocyclic ring dynamics.     

Differential Inhibition of T Lymphocyte Proliferation and Cytokine Synthesis by [6]‐Gingerol, [8]‐Gingerol,and [10]‐Gingerol

[6]‐Gingerol, [8]‐gingerol, and [10]‐gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]‐gingerol, [8]‐gingerol, and [10]‐gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)‐2 receptor signaling. All three gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon‐γ synthesis. In contrast, only [8]‐gingerol and [10]‐gingerol inhibited CD25 and CD69 expression, and IL‐2 synthesis. None of the gingerols affected IL‐4 synthesis. Exogenous IL‐2 enhanced T lymphocyte proliferation in the presence of [6]‐gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]‐gingerol or [10]‐gingerol. In line with this finding, [8]‐gingerol and [10]‐gingerol impaired IL‐2‐induced proliferation of CTLL‐2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL‐2 receptor signaling. In general, [10]‐gingerol and [8]‐gingerol were more potent inhibitors of T lymphocytes than [6]‐gingerol. Suppression of T lymphocyte responses by gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.     

7-(香豆素-3-甲酰胺)-3-[1-(取代）吡啶基甲基]头孢菌素的合成

 目的：探讨3'-乙酰氧基被N-7亲核试剂取代的反应条件、分离精制方法和新头孢菌素的体外抗菌活性。方 法：7-(香豆素-3-甲酰胺)头孢菌素在Nal或KSCN的存在下与吡啶和β-甲基吡啶反应，产物用大孔吸附树脂及葡 聚糖凝胶柱层析分离。结果：合成的二个新头孢菌素化合物，由红外光谱、元素分析和核磁共振谱确证其化学结构。体外抗菌试验表明，对某些革兰阴性菌有一定的抑菌作用。结论：该反应中加入大量的Nal可缩短短反应时间并减少杂质。大孔吸附树脂可有效果将头孢菌素与无机盐分离。     

7－（香豆素－3－甲酰胺）－3－［1－（取代）吡啶基甲基］头孢菌素的合成

目的：探讨３＇－乙酰氧基被Ｎ－亲核试剂取代的反应条件、分离精制方法和新头孢菌素的体外抗菌活性。方法：７－（香豆素－３－甲酰胺）头孢菌素在ＮａＩ或ＫＳＣＮ的存在下与吡啶和β－甲基吡啶反应，产物用大孔吸附树脂及葡聚糖凝胶柱层析分离。结果：合成的二个新头孢菌素化合物，由红外光谱、元素分析和核磁共振谱确证其化学结构。体外抗菌试验表明，对某些革兰阴性菌有一定的抑菌作用。结论：该反应中加入大量的ＮａＩ可缩短反应时间并减少杂质。大孔吸附树脂可有效地将头孢菌素与无机盐分离。     

增液承气汤治疗5-HT3受体拮抗剂所致便秘的临床研究

目的：观察增液承气汤治疗5-HT3受体拮抗剂所致便秘的疗效,同时观察增液承气汤的增效减毒作用。方法：选择符合纳入标准的肿瘤病例200例,随机分为治疗组和对照组各100,治疗组给予中药增液承气汤,对照组给予福松,比较两组疗效及其他观察指标。结果：与对照组相比较,治疗组可显著提高治疗便秘的治愈率（P＜0.05）;对其他伴随症状也均具有显著性改善（P＜0.05;P＜0.001,食欲不振除外）;治疗后生存质量评分情况,90分以上患者显著增加。结论：增液承气汤是治疗5-HT3受体拮抗剂所致便秘的有效方剂,同时提高了5-HT3受体拮抗剂的止吐效果,明显改善了其他伴随症状,提高了患者生活质量。     

Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae)

In our screening program for antihypertensive properties of plants, the leaves of Ailanthus excelsa (Roxb), a plant used in Egyptian traditional medicine, were analysed. Chromatographic separation of A. excelsa MeOH extract yielded six flavonoids for the first time from this species, namely apigenin, luteolin, kaempferol-3-O-alpha-arabinopyranoside, kaempferol-3-O-beta-galactopyranoside, quercetin-3-O-alpha-arabinopyranoside and luteolin-7-O-beta-glucopyranoside. The in vitro hypotensive activities of the MeOH extract and the isolated compounds were elucidated. All the flavonoids tested exhibited ACE inhibitory activity, in particular the most active compound was kaempferol-3-O-beta-galactopyranoside with an IC(50) value of 260 microm.     

Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum

Peppermint oil (Mentha × piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT(3) receptors (serotonin receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site.     

Inhibition by chlorophyllin of forward and reverse bacterial mutagenicity of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide

Chlorophyllin (CHL), a water soluble derivative of the green pigment chlorophyll, was evaluated for its antimutagenic activity towards benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). CHL suppressed dose-dependently the formation of 8-azaguanine-resistant mutant colonies in Salmonella typhimurium TM677 treated with BPDE. Under the same experimental conditions, the cytotoxicity of this direct-acting mutagen was concomitantly blunted by CHL. The protective effect of CHL against BPDE mutagenicity was confirmed in the Salmonella histidine⁺ reversion assay CHL also reduced the in vitro covalent binding of BPDE to DNA. Copyright © 1998 John Wiley & Sons, Ltd.     

6-�л�-3-����-7H-����[3,2-b]-1,2,4-���-7-ͪ�໯����ĺϳɼ�������������ø���ƻ���

??OBJECTIVE To explore the synthesis and acetylcholinesterase inhibitory activity of 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. METHODS Benzaldehyde and acetylglycine were used as raw materials and underwent Erlenmeyer-Pl??chl reaction, condensation reaction, hydrolysis reaction, condensation reaction to obtain 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-ones derivatives. The derivatives reacted with substituted ??-phenacyl chlorides to generate 6-benzyl-3-(hydroxylaryl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones derivatives. Then, Williamson reaction was used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones as target compounds. RESULTS Nine 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones were prepared as target compounds. All target compounds exhibited inhibitory activities against human AChE in vitro, five of which had inhibitory rates above 50% at 10 ??mol??L^-1. CONCLUSION Based on the screening results of AChE inhibitory activity in vitro and docking studies, there are some interactions between 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives and the anionic binding site and PAS zones of AChE, and the target compounds have exhibited AChE inhibitory activities.     

HPLC测定N-[2-(5-甲氧基-1H-吲哚-3-)乙基]己酰胺的含量及其有关物质

 目的建立了N-[2-(5-甲氧基-1H-吲哚-3-)乙基]己酰胺(MLT-5)含量测定和有关物质检查的方法。方法采用Zorbax300SB C₁₈(4.6mm×250mm,5μm)色谱柱,流动相为甲醇-水(55∶45),流速1.0mL·min^-1,检测波长277nm。结果在所选定的液相色谱条件下,有关物质与主药完全分离,MLT-5在0.05～40mg·L^-1(r=0.9997)内线性关系良好,最低检测限为0.4ng。检测了3批样品,主峰含量均在99.0%以上,有关物质在1%以内。结论此法简便、灵敏、准确,可用于MLT-5的含量测定和有关物质检查。     

含有取代哌嗪及哌啶结构的噻吩并吡啶类化合物的合成及活性研究

 目的 设计合成一系列新型的含取代哌嗪及哌啶的噻吩并吡啶类衍生物,并对其体内抗血小板聚集活性进行了初步评价。 方法 从噻吩并吡啶 ( 1 ) 出发,与氯乙酰氯连接得到关键中间体（ 2 ）,再与一系列取代哌嗪及哌啶连接得到目标化合物（ 3-19 ）。 结果 得到 17 个新化合物,所有化合物结构都经过 ¹ H NMR 及质谱确证。这些化合物都进行了大鼠体内抑制血小板聚集活性测试。其中化合物 10-14 具有较高活性。 结论 该类噻吩并吡啶衍生物有可能成为新型结构的具有抗血小板聚集活性的先导化合物,值得进一步研究。     

Seco[D-Asp3]microcystin-RR and [D-Asp3,D-Glu(OMe)6]microcystin-RR, two new microcystins from a toxic water bloom of the cyanobacterium planktothrixrubescens

Two novel microcystins, seco[d-Asp(3)]microcystin-RR (1) and [d-Asp(3),d-Glu(OMe)(6)]-microcystin-RR (2), along with the known [d-Asp(3)]microcystin-RR (3), were isolated from a Planktothrix rubescens toxic bloom collected in Lake Bled, Slovenia. The structures were deduced using one- and two-dimensional NMR techniques, ESIMS/CID/MS analysis, and Marfey's method for determining the amino acids' absolute stereochemistry. Compounds 1 and 3 exhibit weak PP1 inhibitory activity. The NMR data of compound 3 are reported here for the first time.