Isolation and Chemical Transformations of Vasicinone

Vasicinone and peganine were isolated from Peganum harmala L. Vasicinone 2,4-dinitrophenylhydrazone and vasicinone ketal were prepared.     

新型鸭嘴花碱衍生物的合成及其抗炎活性评价

鸭嘴花碱是从傣药鸭嘴花中分离出来的一种具有多种生物活性的生物碱。对鸭嘴花碱进行结构修饰,经取代和Huisgen反应合成了7个未见文献报道的含三唑取代的鸭嘴花碱衍生物(2a~2g),其结构经1HNMR和13CNMR表征。以地塞米松作阳性对照,采用细菌脂多糖诱导小鼠巨噬细胞RAW264.7模型对衍生物的体外抗炎活性进行了筛...     

Alkaloids ofNitraria komarovii. XV. Vasicinone and deoxyvasicinone N-oxides

Two new alkaloids have been isolated from the epigeal part ofNitraria komarovii — the N-oxides of vasicinone and of deoxyvasicinone. Their structures have been established on the basis of spectral results and chemical transformations.     

Alkaloids ofNitraria komarovii. XV. Vasicinone and deoxyvasicinone N-oxides

Two new alkaloids have been isolated from the epigeal part ofNitraria komarovii — the N-oxides of vasicinone and of deoxyvasicinone. Their structures have been established on the basis of spectral results and chemical transformations.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 580–582, July–August, 1993.     

Multifunctional Receptor with Tunable Selectivity: A Comparative Recognition Profile of Organic Nanoparticles with Carbon Dots

The exponential growth in the research field of water pollution control demands the evolution of novel sensing materials for regulation and quantification of metals ions. Within this context, the current work reports a new strategy for the synthesis of carbon dots from the hydrothermal treatment of organic nanoparticles. The organic nanoparticles are found to be selective towards Cs(I) ions with a detection limit of 5.3 nM, whereas the highly fluorescent carbon dots are found to be selective towards Ag(I) ions with a detection limit of 4.8 nM. Both sensing systems illustrate rapid sensing with a working pH range from 4–9. The interfacial molecular restructuring of the sensing systems in the aqueous phase has been investigated in the absence and presence of targeted metal ions using a sum frequency generation vibrational spectroscopic tool. The practical applicability of the sensors was checked in environmental samples. This work opens new avenues for the exploration of temperature‐guided sensing modulation in nanomaterials.     

The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.     

Synthesis of Optically Active Vasicinone Based on Intramolecular Aza-Wittig Reaction and Asymmetric Oxidation(1)

Both optical isomers of a quinazoline alkaloid, vasicinone, were synthesized by two different methods. The first method used (3S)-3-hydroxy-gamma-lactam as a chiral synthon, which was, after O-TBDMS protection, o-azidobenzoylated followed by treatment with tri-n-butylphosphine to afford (S)-(-)-vasicinone via the tandem Staudinger/intramolecualr aza-Wittig reaction. The second method utilized asymmetric oxygenation of deoxyvasicinone with (1S)-(+)- or (1R)-(-)-(10-camphorsulfonyl)oxaziridine (the Davis reagent), respectively. The aza-enolate anion of deoxyvasicinone was treated with (S)-(+)-reagent to afford (R)-(+)-vasicinone in 71% ee, while the reaction with (R)-(-)-reagent gave (S)-(-)-vasicinone in 62% ee. The optical purity was analyzed by HPLC on specially modified cellulose as a stationary phase. These results provided a facile method to prepare both optical isomers of vasicinone and confirmed the recently reversed stereochemistry of natural (-)-vasicinone.     

Comparative Pharmacokinetics and Relative Bioavailability of a New Anxiolytic GML-1 in Tablet Form

Moscow University Chemistry Bulletin - An open, single, crossover, pharmacokinetic study of GML-1 (dose 50 mg/kg) in rabbits after its oral administration in tablets and alone as a substance is...     

The Biological Fate of a Novel Anticancer Drug Candidate TNBG-5602: Metabolic Profile,Interaction with CYP450, and Pharmacokinetics in Rats

TNBG-5602, a novel anticancer drug candidate, may induce the expression of PPARγ, causing targeted lipotoxicity in cancer tissues. In this study, the in vivo metabolism in rats, in vitro metabolism in recombinant cytochromes, molecular docking for the CYP binding site, and pharmacokinetics in rats were explored to better understand TNBG-5602′s in vivo fate and behavior. Thirteen metabolites were identified using a high-resolution mass spectrometry method, and metabolizing pathways of TNBG-5602 were proposed. Results suggest that TNBG-5602 could be metabolized by CYP450s, while CYP2D6 may play an important role in its in vivo metabolism. The main metabolizing sites of TNBG-5602 are the amino group on the side chain and rings A and E in the molecule. TNBG-5602 is a potent CYP2D6 inhibitor, with an IC₅₀ value of 2.52 μM. An interaction responsible for its metabolism is formed by the NH on the side chain bonding with the ASP301 on the CYP2D6. The pharmacokinetics in rats after a single intravenous administration were fitted to a two-compartment model. The clearance was 0.022 L min⁻¹, and the elimination half-life was 710.9 min. The distribution volume of the peripheral compartment was 1.88-fold that of the central compartment, while the K₁₂ was 1.5-fold that of K₂₁. In conclusion, these studies have not only revealed the metabolizing pathways of TNBG-5602 using in vivo and in vitro methodology, but they have also provided the pharmacokinetic characteristics of TNBG-5602 in rats. The results suggest that TNBG-5602 has good drug developability in terms of pharmacokinetic behaviors.     

Nanoparticles of calcium hydroxide for wood conservation. The deacidification of the Vasa warship

The seventeenth century Swedish warship Vasa represents a unique case in the study of ancient wrecks and a challenge for finding new methods for artifacts conservation. The presence of sulfuric acid inside the wooden structure of Vasa is one of the possible causes of chemical damage of the wood. During recent investigations, pH values below 2 were observed inside the wreck in several places. Neutralization treatments temporarily raised the surface pH about 6 units, but after a few months the pH reverted back to original values. In this study we show that wood from the Vasa warship can be deacidified by using a dispersion in 2-propanol of calcium hydroxide nanoparticles. These particles can penetrate into the wood allowing a very efficient deacidification. Alkaline nanoparticles are converted into calcium sulfate without mechanical stress to the wood's lumens. Additional applications produce an excess of alkaline nanoparticles that are converted into carbonate, an alkaline reservoir to protect the wood from further acid attack. Artificial aging of Vasa wood demonstrates that nanoparticles facilitate protection of wood toward further acid degradation.     

Comparative Analysis of the Phenolic Profile of Lycium barbarum L. Fruits from Different Regions in China

Lycium barbarum L. (LB) fruits have high nutritive values and therapeutic effects. The aim of this study was to comprehensively evaluate the differences in phenolic composition of LB fruits from different geographical regions. Different methods of characterization and statistical analysis of data showed that different geographic sources of China could be significantly separated from each other. The highest total phenolic compound (TPC) content was observed in LB fruits from Ningxia (LBN), followed by those from Gansu (LBG) and Qinghai (LBQ). The Fourier transform infrared (FTIR) spectra of LB fruits revealed that LBQ had a peak at 2972 cm⁻¹ whereas there was no similar peak in LBG and LBQ. A new HPLC method was established for the simultaneous determination of 8 phenolic compounds by quantitative analysis of multiple components by a single marker (QAMS), including 4 phenolic acids (chlorogenic acid, caffeic acid, 4-hydroxycinnamic acid, and ferulic acid), 1 coumarin (scopoletin), and 3 flavonoids (kaempferol-3-O-rutinoside, rutin, and narcissoside). It was showed that rutin was the most dominant phenolic compound in LBQ, although the average content of 4 phenolic acids was also high in LBQ, and scopoletin was the richest in LBG. UHPLC-Q-TOF-MS was used to qualitatively analyze the phenolics, which showed LBN was abundant in phenolic acids, LBQ was rich in flavonoids, and coumarins were the most plentiful in LBG. In conclusion, this study can provide references for the quality control and evaluation of phenolics in LB fruits and their by-products.     

溴的药物动力学及药效动力学

本世纪以来,含溴药物及其临床应用的研究得到了空前的发展,在2001-2010年十年间,有关含溴药物的药物动力学和药效动力学中文文献数亦占相关文献总数的80％左右,目前研究的药物主要集中于呼吸系统用药和神经肌肉阻断药.综述了溴化物的生物半衰期、8种药物的药物动力学和5种药物的药效动力学研究概况.     

Oligomerization Profile of Human Transthyretin Variants with Distinct Amyloidogenicity

One of the molecular hallmarks of amyloidoses is ordered protein aggregation involving the initial formation of soluble protein oligomers that eventually grow into insoluble fibrils. The identification and characterization of molecular species critical for amyloid fibril formation and disease development have been the focus of intense analysis in the literature. Here, using photo-induced cross-linking of unmodified proteins (PICUP), we studied the early stages of oligomerization of human transthyretin (TTR), a plasma protein involved in amyloid diseases (ATTR amyloidosis) with multiple clinical manifestations. Upon comparison, the oligomerization processes of wild-type TTR (TTRwt) and several TTR variants (TTRV30M, TTRL55P, and TTRT119M) clearly show distinct oligomerization kinetics for the amyloidogenic variants but a similar oligomerization mechanism. The oligomerization kinetics of the TTR amyloidogenic variants under analysis showed a good correlation with their amyloidogenic potential, with the most amyloidogenic variants aggregating faster (TTRL55P > TTRV30M > TTRwt). Moreover, the early stage oligomerization mechanism for these variants involves stepwise addition of monomeric units to the growing oligomer. A completely different behavior was observed for the nonamyloidogenic TTRT119M variant, which does not form oligomers in the same acidic conditions and even for longer incubation times. Thorough characterization of the initial steps of TTR oligomerization is critical for better understanding the origin of ATTR cytotoxicity and developing novel therapeutic strategies for the treatment of ATTR amyloidosis.     

Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile

The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol^® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (X_exp = 2.30 × 10³, 3.08 × 10⁴, 2.90 × 10⁴) at 323.15 K, its mixture (X_exp = 1.93 × 10³, 1.89 × 10⁴, 1.58 × 10⁴) at 298.15 K, and 1,4-dioxane (w) + water (1−w) mixture ratio of w = 0.8 (X_exp = 3.74 × 10³) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD ≤ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG° vs ΔH° at 0.70 < x₂ < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule’s properties.     

From the Micro- to the Macro-: Managing the Conservation of the Warship,Vasa

Sweden's famous warship, Vasa, sank on her maiden voyage in August 1628, and remained on the bottom of Stockholm harbour for 333 years. Raised in 1961, she became the first large-scale wooden object to be treated with polyethylene glycol (PEG). In the summer of 2000 a number of acidic salt precipitations were noticed on the surface of the ship and on wooden artefacts in the storerooms. An international research project has been established to look into the causes of this problem and suggest possible re-treatments. Meanwhile projects are underway to monitor movements in the ship, to build a better support system, and to replace the thousands of iron bolts holding the structure together, while a sophisticated new climate system has recently been installed in the museum.     

Chemical Profile of Danning Tablets by LC-DAD Coupled with ESI-MS

HPLC-DAD coupled to an electrospray tandem mass spectrometer (ESI-MS) has been developed to analysis the chemical profile of Danning tablets. Separation was performed on a ZORBAX Extend C₁₈ analytical column by gradient elution with acetonitrile and formate buffer (containing 12.6 mmol L⁻¹ formic acid, adjusted to pH 5.0 with ammonia) at a flow rate of 0.8 mL⁻¹ min. Twenty-three peaks were identifies as the major compounds in this preparation. Similarity measurements of the HPLC-UV chromatograms were investigated by a Similarity Evaluation System for Chromatographic Fingerprinting of Traditional Chinese Medicine (TCM) in the range of 0.84–0.99, and principal components analysis (PCA) on the quantitative analysis data was further performed to evaluate the variation among batches. The proposed method gives chemical profiles of multi-components in one run, and therefore can be readily utilized as a comprehensive quality control approach for TCM.     

富含羧基的球形介孔分子筛SBA-15的合成及药物释放性能

本文采用原位合成法合成了富含羧基的SBA-15球形介孔分子筛. 研究了修饰剂（三烷氧基氰乙基硅烷 CTES）的用量对介孔分子筛SBA-15形貌、孔径及BET比表面积的影响. 用粉末X射线衍射(XRD)、扫描电镜(SEM)、红外（IR）和氮气吸附/脱附对样品进行了详细的表征. 该材料展示了尺寸在0.5-1 μm规则的球形形貌、有序的二维六方相介孔结构、较大的比表面积和孔容、并且随着修饰剂用量的增加, SBA-15的孔径变小, 比表面积下降. 药物组装及缓释性能测试表明, 该材料具有较好的药物组装及缓释释放性能. 该材料在催化、药物载体和色谱分析填料等领域将具有潜在的应用.     

Determination and Pharmacokinetics of Mexiletine in Rabbit Plasma by Gas Chromatography with Mass Spectrometry

This paper describes a gas chromatography/mass spectrophotometry method for determination of mexiletine in rabbit plasma. Mexiletine and internal standard metoprolol were extracted from rabbit plasma with a mixture of ethylacetate and diethylether at basic pH with liquid-liquid extraction. Calibration curves were linear over the concentration range 45–2000 ng/mL. Intra- and inter-day precision (relative standard deviation) for mexiletine in rabbit plasma were less than 6.9%, and accuracy (relative error) was better than 6.8%. Recovery of mexiletine from rabbit plasma averaged 92.6%. This method was successfully applied to six rabbits which had given an oral capsule of 200 mg mexiletine.     

Pharmacokinetics and Tissue Distribution Study of Tryptanthrin in Rats by RP-HPLC with DAD Detector

A simple RP-LC-UV method was established for the determination of tryptanthrin in plasma and different tissues of rats. The separation was achieved by HPLC on a C₁₈ column with a mobile phases composed of acetonitrile–water (47:53, v/v), UV detection was used at 251 nm. Good linearity was found between 0.0183–1.1712 μg mL⁻¹ (r ² = 0.999) for plasma and 0.0937–1.7568 μg mL⁻¹ for the tissue samples, respectively (r ² ≥ 0.9932). The intra- and inter-day precisions expressed as the relative standard deviation for the method were 0.92–6.01 and 1.06–9.11 %, respectively. The relative recoveries of tryptanthrin ranged from 95.26 to 97.89 % for plasma and 82.55 to 114.99 % for tissue homogenates (except heart). The developed method was successfully applied to the pharmacokinetics and tissue distribution research after orally administration of a 56-mg kg⁻¹ dose of tryptanthrin to healthy SD rats. The main pharmacokinetics distribution results showed that liver, lung, small intestine, and large intestine were the major distribution tissues of tryptanthrin in rats, and that tryptanthrin had difficulty in crossing the blood–brain barrier.