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1.
四倍体板蓝根中的两个新生物碱 总被引:22,自引:0,他引:22
目的 研究四倍体菘蓝Isatis indigotica Fort.根的化学成分。方法 应用硅胶柱色谱对乙酸乙酯萃取部分中化学成分进行分离纯化,根据理化常数测定和光谱(IR, MS, 1HNMR, 13CNMR, 2DNMR)分析技术鉴定结构。 结果 从乙酸乙酯萃取部位分离得到4种生物碱类化合物,分别鉴定为:色胺酮(I), 2,5-二羟基吲哚(II), 2,3-二氢-4-羟基-2-氧-吲哚-3-乙腈(III),吲哚-3-乙腈-6-O-β-D-葡糖苷(IV)。结论 II为首次从该种植物中分离得到,III,IV为新化合物。 相似文献
2.
本文报道十二种四氢异喹啉类生物碱对大鼠脑内D-2,5-HT1和5-HT2受体的结合特性。其中l-千金藤碱(l-STP)对这三种受体均有较高的亲和力,其Ki值分别为1.7×10-7,9.4×10-8和1.8×10-7mol。l-莲碱(l-REM)对5-HT2受体的亲和力与Z-STP相似(Ki=1.7×10-7mol)。THB,THC和THJ对D-2受体的亲和力介于l-SPD和l-THP之间。本文报道的多数生物碱能同时影响两种或两种以上受体部位的结合特性,提示它们对单胺神经系统可能有复杂的相互作用。 相似文献
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氟哌啶醇对大鼠离体海马脑片和原代神经元缺糖/缺氧和N-甲基-D-天冬氨酸损伤的保护作用 总被引:3,自引:0,他引:3
目的观察氟哌啶醇对大鼠离体海马脑片和原代神经元的缺糖/缺氧(OGD)和N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)损伤的潜在保护作用及其机制。方法海马脑片OGD以无葡萄糖的人工脑脊液中通95% N2+5% CO2诱导。通过测定TTC染色后形成的红色产物来分析脑片活性。结果氟哌啶醇(1和10 μmol·L-1)抑制OGD损伤,抑制率分别为17.7%和25%,而D2多巴胺受体拮抗剂多潘立酮无此作用。NMDA也能显著降低海马脑片及原代神经元的活性,而氟哌啶醇可抑制这一损伤作用。结论氟哌啶醇对大鼠离体海马脑片OGD和原代神经元NMDA损伤有保护作用。 相似文献
6.
中国辽宁栽培西洋参化学成分的研究 总被引:4,自引:0,他引:4
中国辽宁栽培西洋参(Panax quinquefolius Linn)的总皂甙用低压硅胶柱和反相Rp18Labar柱层析分离得到18种化合物,用IR,MS(FD-MS,FAB-MS),13C-NMR及化学方法鉴定了16种化合物的化学结构;分别为棕榈酸(1),齐墩果酸(2),胡萝卜甙(daucosterin 3),人参皂甙-Rh1(4),—Rg3(5),—Rg2(6),—Rg1(7),—Rf(8),—Re(9),—Rd(10),—Rb2(11),—Rb1(12)、—R0(13),蔗糖(14),人参三糖(15)及一种新皂甙(16),结构为:20(s)原人参二醇-3-[-O-β-D-吡喃糖基(1→2)β-D-葡萄吡喃糖基(1→2)β-D-葡萄吡喃糖基],20-[-O-β-D-葡萄吡喃糖基(1→6)β-D-葡萄吡喃糖甙,命名为人参皂甙-RAO(ginsenoside-RA0)。化合物(4)和(5)系首次从西洋参中分离出的已知皂甙。 相似文献
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温敏性吲哚美辛/β-环糊精包合物的制备及体外评价 总被引:4,自引:0,他引:4
目的合成兼具温敏性及药物包合能力的新型药物载体聚(N-异丙基丙烯酰胺)-β-环糊精(PNIPA-β-CD),以吲哚美辛为模型药物,考察该载体的释药行为。方法末端带羧基的PNIPA与改性后的环糊精衍生物在1-(3-二甲氨基丙基)-3-乙基-碳二亚胺(EDC)的作用下缩合,得到PNIPA-β-CD,采用冻干法制备吲哚美辛/PNIPA-β-CD包合物。红外、1H NMR和DSC表征载体的结构及包合物的形成;用分光光度法测定载体材料的LCST,并进行包合物体外释药研究。结果PNIPA-β-CD在35 ℃发生相转变,吲哚美辛/PNIPA-β-CD包合物的载药量为5.8%,药物与载体摩尔比为0.97∶1。体外释放研究表明吲哚美辛/PNIPA-β-CD包合物在37 ℃的释药比其在25 ℃的释放要慢,在LCST以上具有一定的缓释作用。结论该载体既具有温敏性,又具有药物包合作用,并且在体温条件下具有缓释作用,是一种新型的温敏性药物载体。 相似文献
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通光散藤茎的C21甾体成分 总被引:3,自引:0,他引:3
为了研究通光散藤茎中的C21甾体类成分,采用不同的色谱方法对通光散藤茎乙醇提取物进行分离纯化,并用波谱学的方法鉴定化合物的结构。从氯仿部位共分离得到8个C21甾体类化合物,其结构分别被鉴定为11α-O-tigloyl-17β-tenacigenin B (1)、 17β-tenacigenin B (2)、 tenacigenoside A (3)、 11α-O-2-methylbutyryl-12β-O-acetyl tenacigenin B (4)、 tenacissoside H (5)、 marsdenoside A (6)、 tenacissoside G (7)和tenacissoside I (8)。其中化合物1为新化合物。 相似文献
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新型含二硫键和硫酯键的乙酰半胱氨酸衍生物的合成与抗肝损伤活性评价 总被引:1,自引:1,他引:0
目的 设计、合成N-乙酰半胱氨酸衍生物,并评价目标化合物对H2O2诱导的LO2细胞氧化损伤的保护作用。方法 以L-半胱氨酸和N-乙酰半胱氨酸为起始原料,采用酰氯酯化法合成具有全新结构的乙酰半胱氨酸衍生物;以H2O2损伤LO2人肝细胞建立体外氧化损伤模型,利用CCK-8法检测不同浓度H2O2对LO2细胞存活率的影响,并检测细胞上清中MDA含量和SOD活性。结果 共合成了6个全新结构的N-乙酰半胱氨酸衍生物,其结构经1H-NMR、13C-NMR、ESI-MS确证,目标化合物能够抑制H2O2诱导的LO2氧化损伤,并能够降低MDA含量和提高SOD活性(P<0.01或P<0.05)。结论 本研究快速、高效地合成了N-乙酰半胱氨酸系列衍生物,目标化合物对体外肝细胞损伤具有保护作用。 相似文献
10.
极谱法研究辅酶Q10与β-环糊精的包结行为 总被引:1,自引:0,他引:1
目的研究辅酶Q10与β-环糊精(β-CD)的包结行为。方法用极谱法考察主体分子β-CD与电活性客体分子辅酶Q10发生包结反应时,包结物还原波峰电流随时间的变化,峰电位随β-CD浓度的变化,并在自然光照条件下分别考察辅酶Q10和包结物的还原波峰电流随时间的变化。结果在0.1 mol·L-1 HAc/NaAc (pH 4.7)的乙醇-水(60∶40)介质中,辅酶Q10与β-CD形成1∶1的包结物,测得其包结常数kf为1.26×104 L·mol-1,包结反应的表观速率常数k为6.64×10-2 min-1。并测得辅酶Q10的光降解表观速率常数k为7.77×10-3 min-1,辅酶Q10-β-CD包结物的k为3.38×10-3 min-1。结论辅酶Q10和β-CD可形成包结物,并在一定程度上提高了辅酶Q10的光稳定性。 相似文献
11.
LUIS CONSTANTINO JIM ILEY 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(4):409-416
1. The aim was to set out to establish the complete network of metabolites arising from the phenobarbital-treated rat liver microsomal oxidation of N,N-diethyl-m-toluamide (DEET). The products formed from DEET and all its subsequent metabolites were identified by HPLC retention times, UV spectroscopy, mass spectrometry and by comparison with authentic standards. 2. DEET (1a) produces three major metabolites, N-ethyl-m-toluamide (1b), N,N-diethyl-m-(hydroxymethyl)benzamide (2a) and N-ethyl-m-(hydroxymethyl)benzamide (2b), and, at low substrate concentrations or extended reaction times, two minor metabolites, toluamide (1c) and N,N-diethyl-m-formylbenzamide (3a). 1b and 2a are primary metabolites and their formation follows Michaelis-Menten-type kinetics. At low DEET concentrations, ring methyl group oxidation is favoured; at saturation concentrations, methyl group oxidation and N-deethylation proceed at similar rates. The rate of formation of 2b decreases with increasing DEET concentration; 2b is therefore a secondary metabolite of DEET and DEET acts as a competitive inhibitor of the metabolism of 1b and 2a. 3. Except for the primary amides, where N-dealkylation is impossible, metabolism of all subsequent compounds, 1b,c, 2a-c, 3a-c and 4a,b, involves an N-deethylation (NEt2 → NHEt or NHEt → NH2) competitive with a ring substituent oxidation (CH3 → CH2OH, CH2OH → CHO or CHO → CO2H). Surprisingly, the aldehydes 3a-c are also reduced to the corresponding alcohols 2a-c (CHO → CH2OH); CO inhibits the oxidative metabolism of 3a-c, but reduction to 2a-c continues uninhibited. 4. The outcomes of this work are that (1) previously unreported aldehydes 3b and 3c form part of the DEET network of metabolites, (2) the reduction of the aldehydes 3a-c has the potential to inhibit the formation of the more highly oxidized DEET metabolites, (3) amide hydrolysis was not observed for any substrate and (4) no evidence was obtained for N-(1-hydroxyethyl)amide intermediates. 相似文献
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Tyrosine, tyrosine peptides and derivatives, in total 11 species, were selected as models for the study of optical properties (1Lb band of phenolic group) and side-chain arrangement (rotamers around Cα – Cβ bond) of tyrosine as a function of chemical structure and pH effects. Circular dichroism spectra between 240 and 320 nm and n.m.r. spectra were recorded for the different ionization states. Results are discussed in terms of charge effects from N- and C-terminal groups and local conformation influence on 1Lb band of the phenolic chromophore and on distribution of rotamer populations in side-chain of tyrosine. Fractions of rotamer populations were estimated from α-β proton-proton coupling constants and, in the cases of tyrosine and N-acetyl-tyrosine, from 15N-β nitrogen-proton coupling constants, which allow the stereospecific assignment of the β and β′ protons. The rotamer populations of tyrosine, averaged from all the data of the samples in solution, were then compared with their statistical distribution in the solid state. Interestingly, agreement is excellent when we refer to crystal of tyrosine, tyrosine derivatives or small peptides (31 samples) and poor in the case of proteins. This leads to a discussion on both the validity of using statistical distributions of rotamers in proteins as reference for rotamer preferences inside small peptides in solution and the choice of the appropriate Jg and Jt values in Pachler's approach. The possible existence of a correlation between ellipticity and rotamer populations for such samples is examined. 相似文献
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Silvio Cerrini Walter Fedeli Gino Lucente Fernando Mazza Francesco Pinnen GIancarlo Zanotti 《Chemical biology & drug design》1984,23(3):223-229
N-(N-phenylacetyl-L-alanyl)-cyclo-(L-phenylalanyl-D-prolyl) (I) was synthesized in one step starting from the linear precursor phenylacetyl-L-alanyl-L-phenyl-alanyl-L-proline. X-ray crystallographic analysis of (I) shows that the diketopiperazine ring adopts a boat conformation appreciably more puckered than that found in the unacylated cyclo(L-Pro-D-Phe). The side chain of Phe residue is in quasi-axial flagpole orientation with the aromatic ring folded over the diketopiperazine ring. 1H-n.m.r. data indicate that the same conformation is preferred in chloroform solution. The proline ring assumes a β-envelope conformation. No intramolecular interactions between the diketopiperazine system and the aromatic ring of the N-phenylacetyl-alanyl side chain have been evidenced. Crystals: space group P21 with a= 9.956(3), b= 8.809(2), c= 13.615(2) Å, β= 111.0(1)° and Z = 2. The final R and Rw are 0.037 and 0.052, respectively. 相似文献
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The crystal structure of a tripeptide, l -phenylalanyl-glycyl-glycine (C13H17,N3O4), molecular weight = 279.3, has been determined. The crystals are orthorhombic, space group P 212121, with a= 5.462(1) A, b= 15.285(5), c= 16.056(4), Z = 4 , and P(calc) = 1.384 g. cm-3. The final R-index is 0.052 for 866 reflections with θ/λ≤ 0.55 A-1 and 1 > σ. The molecule exists as a zwitterion, with the N-terminus protonated and the C-terminus in an ionized form. Both the peptide units are in the trans configuration and planar, though one of them shows significant deviations from planarity (|Δ| = 5.1°). The peptide backbone is folded, with the torsion angles of ψ1= 116.2(5)°, ψ31= 178.8(4), φ2=?89.7(5), ψ2=?28.9(6), ω2=?174.9(4), φ3= 134.9(5), ψ31= 7.8(6), ψ32=?172.6(4). The terminal glycine adopts a “d -residue” conformation. For the sidechain of phenylalanine, χ1= 175.5(4), χ2= - 127.0(6). 相似文献
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NADH-supported reduction of tertiary amine N-oxides in rat liver microsomes was investigated with imipramine N-oxide, tiaramide N-oxide and N, N-dimethylaniline N-oxide as substrate in the presence of NADH. The reductase activity is sensitive to carbon monoxide. NADH-cytochrome b5 reductase or cytochrome b5, solubilized by trypsin or subtilisin, showed no N-oxide reductase activity. The NADH-dependent reduction of tertiary amine N-oxides was markedly inhibited by antibody to NADH-eytochrome b5 reductase and antibody to cytochrome b5. These results confirmed that NADH-dependent N-oxide reduction was catalyzed by cytochrome P-450 and the reducing equivalent for the N-oxide reduction was transferred from NADH to cytochrome P-450 mainly via NADH-cyto-chrome b5 reductase and cytochrome b5 in the microsomal membranes. NADH-dependent N-oxide reductase is also sensitive to oxygen and 4 μM oxygen gave 50 per cent inhibition with imipramine N-oxide. Kinetic study shows that Km values for the reduction of imipramine N-oxide, tiaramide N-oxide and N, N-dimethylaniline N-oxide were 0.05 mM, 0.14 mM and 0.16 mM, respectively. NADH-dependent N-oxides reductase activity is affected by azo and nitroso compounds and hydrazide, although the degree of inhibition was rather weak compared with those of NADPH-dependent activity. Furthermore, NADH-dependent reduction of tertiary amine N-oxide was only slightly affected by n-octylamine, 2,4-diehloro-6-phenylphenoxyethylamine and aniline. NADH-dependent N-oxide reductase activity in liver microsomes was less sensitive to phenobarbital or 3-methyleholanthrene pretreatment than NADPH-dependent activity. Some characteristics of NADH-dependent N-oxide reductase activity were discussed and compared with those of NADPH-dependent activity. 相似文献
16.
Soine William H. Soine Phyllis J. Wireko Fred C. Abraham Donald J. 《Pharmaceutical research》1990,7(8):794-800
The stereochemistry associated with the amobarbital N-glucoside diastereomers (1a and 1b) that are excreted by humans in urine is unknown. Using X-ray crystallography, the absolute configuration of 1b was determined to be S (C-5 position of the barbiturate ring). Following oral administration of amobarbital to Caucasians and Orientals, from 5 to 25% of the dose of amobarbital was excreted in the urine as 1b. The other diastereomer, 1a, accounted for less than 0.1 to 0.2% of the dose in four individuals, with none detected in nine individuals. The rate constants, k
f ,1b, determined from the urinary excretion of lb were lower than those previously reported for unresolved amobarbital N-glucosides. However, based on the urinary excretion of lb, the rate constants, K, for elimination of amobarbital in Caucasians and Orientals were similar to those previously determined from the serum levels of amobarbital and the urinary excretion of unresolved amobarbital N-glucosides. In previous studies of the N-glucosylation of amobarbital, it is likely that a single N-glucose diastereomer, lb, was being observed. 相似文献
17.
R. MILLER N.M. GALITSKY W.L. DUAX D.A. LANGS V.Z. PLETNEV V.T. IVANOV 《Chemical biology & drug design》1993,42(6):539-549
The crystal structures of two solvated forms of ternatin, cyclo[-β-OH-d -Leu-d -Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-d -(NMe)Ala-] are reported. The first crystallizes with two molecules of peptide and one of dioxane in the asymmetric unit: P212121, a = 11.563(1), b = 21.863(2), c = 36.330(4) Å. The second crystallizes with two molecules of peptide and one of water in the asymmetric unit: P212121, a = 14.067(2), b = 16.695(1), c = 36.824(6) Å. N-Methylation of four of the seven residues of ternatin appears to reduce the number of low-energy conformations the molecule can assume. The same H-bonded macrocyclic ring conformation is adopted by the backbone of each of the four molecules observed here. All the amino-acid side chains, with the exception of d -Ile2, have similar orientations in each of the four conformers. The heptapeptide macrocycle is characterized by: (i) a cis peptide between (NMe)Ala3 and (NMe)Leu4, (ii) a type II β-bend, involving residues Leu5-(NMe)Ala6-d -(NMe)Ala7-β-OH-d -Leu2, stabilized by two H-bonds, N1′05 and N5′01, between Leu5 and β-OH-d -Leu1 residues, (iii) a third intramolecular H-bond, observed in each of the four molecules, between the hydroxyl group of β-OH-d -Leu1 and the carbonyl oxygen of d -Ile2. 相似文献
18.
R. Reh J. Ozols B. Clement 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(9):1177-1190
1.?This study investigates the enzymatic reduction of N-hydroxylated amidines by porcine adipose tissue and the possible involvement of stearoyl-CoA desaturase (SCD).2.?The reduction of the model substrate benzamidoxime was studied with porcine adipose tissue microsomes and partially purified SCD from SCD-enriched rat liver microsomes.3.?Inhibitor studies with these microsomal preparations using various inhibitors including anti-SCD antibody, cyanide and stearoyl-CoA supported a role for SCD in the reduction of N-hydroxylated amidines in adipose tissue. The content and activity of SCD in these microsomes was established by Western blot and SCD activity determinations. Additionally, a reconstituted system of cytochrome b5, NADH-cytochrome b5 reductase and partially purified SCD from SCD-enriched rat liver microsomes supported benzamidoxime reductase activity that was inhibitable by an anti-SCD antibody.4.?The results support the participation of SCD in the reduction of amidoxime prodrugs and demonstrate for the first time that SCD can also accept foreign compounds (xenobiotics) as substrates. 相似文献
19.
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(9):780-784
Abstract1. Upamostat (Mesupron®) is a new small molecule serine protease inhibitor. The drug candidate was developed to inhibit the urokinase-type plasminogen activator (uPA) system, which plays a major role in tumor invasion and metastasis. Upamostat is currently in clinical development as an anti-metastatic and non-cytotoxic agent against pancreatic and breast cancer.2. Upamostat is the orally available amidoxime- (i.e. hydroxyamidine-) prodrug of the pharmacologically active form, WX-UK1. In this study, the reductive enzymatic activation of upamostat to its corresponding amidine WX-UK1 was analyzed.3. The recently discovered molybdenum enzyme “mitochondrial Amidoxime Reducing Component” (mARC) catalyses together with its electron transport proteins cytochrome b5 and NADH cytochrome b5 reductase the reduction of N-hydroxylated prodrugs. In vitro biotransformation assays with porcine subcellular fractions and the reconstituted human enzymes demonstrate an mARC-dependent N-reduction of upamostat. 相似文献
20.
Werner Lwe 《Archiv der Pharmazie》1978,311(5):414-420
4-Hydroxy-5-hydroxyimino-7-methyl-5H-pyrano[2,3-b]pyridine 8-Oxide In the course of studies on the reaction between dehydroacetic acid ( 1 ), N,N-dimethylformamide dimethyl acetal and hydroxylamine, a new two-step synthesis of a pyranopyridine with the structure of a vinylogous hydroxamic acid was discovered. The isomeric structures 5a - 8b , derived from the empirical formula C9H8N2O4 are discussed. The existence of 5a in solution is indicated by the spectral data (ms, ir, nmr). 相似文献