QSAR Study and VolSurf Characterization of Human Intestinal Absorption of Druge

The prediction of human intestinal absorption is a major goal in the design,optimization,and selection of candidates for the develoment of oral drugs.In this study,a computerized method(VolSurf with GRID) was used as a novel tool for predicting human intestinal absorption of test compound,and for determining the critical molecular properties needed for human intestinal absorption.The tested molecules consisted of 20 diverse drug-like compounds.Partial least squares(PLS) discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption.A good correlation(r^2=0.95,q^2=0.86) between the molecular modeling results and the experimental data demonstrated that human intestinal absorption could be predicted from the three-dimensional(3D) molecular structure of a compound .Favorable structureal properties identified for the potent intestinal absorption of drugs included strong imbalance between the center of mass of a molecule and the barycentre of its hydrophilic and hydrophobic regions and a definitive hydrophobic region as well as less hydrogen bonding donors and acceptors in the molecule.     

Synthesis of Tetracycline Analogues and Test of Their Affinity on Synthetic Hydroxyapatite

To develop bone target drugs is an attractive field for increasing the potency and selectivity of these drugs in the treatment of osteoporosis and Pagets disease etc. As known, after systematic administration tetracycline can be distributed in bone and bind to hydroxyapatite with high affinity1. Thus we tried to use tetracycline as a bone targeted carrier. However, tetracycline is less stable, and its complex structure bring much difficulty in the coupling reaction and purification of the p…     

Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the ...     

Effect of Dai-Bai-Jie on the proliferation and migration of the A549 cells

Lung cancer is the most malignant tumor disease with the highest diagnosis and mortality rate in China.The development of therapeutic drugs is the current research focus.Dai-Bai-Jie is a traditional medicine of the Dai nationality,which is commonly used in the treatment of decreasing swelling,alleviating pain and detoxification.Most of the current researches focused on the component analysis of Dai-Bai-Jie,but few researches studied on its antitumor and pharmacological effect.In this study,we incubated A549 cells with different concentrations of Dai-Bai-Jie.The cell proliferation experiment showed that the DaiBai-Jie solution inhibited the proliferation of A549 cells and caused cell apoptosis.In this work,we confirmed that Dai-Bai-Jie had an inhibitory effect on the proliferation and migration of non-small cell lung cancer A549,which may be used as a novel candidate of anti-tumor therapy for lung cancer patients.     

Studies on the Structure and Properties of Cordierite Synthesized by Talc-Magnesite

Homogeneous cordierite has been synthesized at low cost by talc-magnesite and coal gangue as the main raw materials. The mechanism of synthesizing cordierite under such a com- posing system of raw materials, and the effect of temperature on the crystal cell parameters and microstructure and thermal expansion coefficient of cordierite crystal have been studied via testing methods of XRD, SEM, etc. The result shows that the homogeneous cordierite can be synthesized by the systematic composing materials of “talc-magnesite—coal gangue—talc” with heat pre- servation at 1350 ℃ for 1 h; as the keeping time is prolonged, Al3+ and Mg2+ in cordierite crystal are replaced by a few impurity ions such as Fe3+, Fe2+, etc., and the crystal cell parameters of cordierite present an increase trend; as the high-temperature heat preservation is prolonged, the content of glassy phase in the sample is increased, its density is improved, and its thermal expansion coeffi- cient presents an increase trend.     

THE PREPARATION OF FRUCTOSE-MODIFIED CHITOSAN MICROCARRIERS AND CULTURE OF PRIMARY RAT HEPATOCYTES

1. INTRODUCTION The development of cell based organs and tissue-engineering devices such as hybrid artificial liver requires a large number of cells be cultured for the replacement of damaged tissue [1,2]. Since its introduction in 1967, microcarriers culture has been applied successfully in growing primary cells and cell lines with the advantage of attaining high cell density [3,4]. Spheroid culture is another promising hepatocytes culture method to enhance the cell density and metaboli…     

An on-chip intestine-liver model for multiple drugs absorption and metabolism behavior simulation

A double-layer microfluidic chip integrated with a hollow fiber(HF)was developed to reconstitute the intestine-liver functionality for studying the absorption and metabolism of combination drugs.Caco-2 cells were inoculated in the HF cavity at the top of the serpentine channel to simulate the intestinal tissue for drug absorption and transport studied,and Hep G2 cells,seeded in the bottom chamber,were used to mimic the liver for metabolism-related studies.Genistein and dacarbazine were selected for combination drug therapy and its effects on cell viability,hepatotoxicity,and cell cycle arrest under drug-conditioned culture were investigated.The results suggested that the combined concentration below-100μg/m L had no significant inhibitory effect on Hep G2 cell viability,and therefore Hep G2 cells maintained their drug metabolism ability.When the drug concentration was increased above 250μg/m L,Hep G2 cells underwent apoptosis.Detection of metabolites by mass spectrometry proved the effective metabolism in the microchip model.This dynamic,co-culture microchip successfully provided a podium for long-term observation of absorption,transport,and metabolism of combination drugs,and could be an effective in vitro simulation model for further clinical research.     

A folic acid-decorated nanoparticles loaded JQ1 for oral squamous cell carcinoma therapy

Oral squamous cell carcinoma(OSCC) is known as one of the most malignant tumors with high recurrence and fatality rate. The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy. Beyond that, a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs. Therefore, we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1) through encapsulating JQ1 [a small-molecule in...     

Caspase-9 Activation—Critical for Betulin-induced Apoptosis of Human Hepatoma Cells

Betulinic acid and its derivatives have been extensively studied in the past for their anti-tumor effects, but relatively little is known about its precursor betulin. In this study we showed that betulin, an abundant natural product, significantly inhibits the cell growth of human hepatoma HepG2 cells in a dose-dependent manner. In the presence of 10 μg/mL betulin, HepG2 cells undergo an apoptosis, as evidenced by apoptotic morphology such as cell shrinkage, membrane blebbing, nuclear condensation and fragmentation, apoptotic body formation, and caspase activation. Ki-netics analysis shows that the depolarization of the mitochondrial membrane potential and the release of the mito-chondrial apoptotic protein cytochrome c occurred as early as 2 h post treatment of HepG2 cells with 10 μg/mL betu-lin. Proteolytic activation of caspase-9, but not caspase-8, was observed in this apoptosis process. Moreover, the in-activation of caspase-9 by its specific siRNA dramatically reduced betulin-induced caspase-3 activation and apoptosis. Taken together, our observations indicate that the activation of caspase-9 is critical for betulin-induced apoptosis of human hepatoma HepG2 cells.     

SYNTHESIS OF MPt/C (M=La, Nd) CATALYSTS BY MICROWAVE RADIATION

1. INTRODUCTION The polymer electrolyte membrane fuel cells (PEMFC) are viewed as one of the most environmentally friendly propulsion system for automotive vehicle in the future, because of its distinct advantages such as high power density, lightweight, low environmental loads and low-temperature operation [1~3]. The biggest challenge for the development of fuel cells for automotive application is reduction of the cost of the cell stack (currently at $500 per kW, while 2004 PNGV goal…     

线叶旋复花化学成份的研究

Xian-Ye-Xuan-Fu-Hua, the flowers of Inula linariaefolia Turcz (Compositae), is a commonly known Chinese medicinal herb and used as expectorant as well as for the treatment of some malignant tumors. The chemical investigation of its active principles by our early work in 1964 resulted in the isolation of a new sesquiterpene lactone (m.p. 190-192`C, (α)D-24 in CHCl3), which possesses significant inhibitory action against Hela cells and fungi in vitro. Besides, it also shows some expectorant activity in preliminary pharmacological tests. Analyses of the spectral data (IR, UV, ^1H NMR, 13C NMR, MS) and our early results of chemical reactions suggested that the compound is the same as britanin 1 (m.p. 192-194`C, (α)D-26 in CHCl3) studied Chugunov in 1971. However its stereochemistry remained unsolved. On careful examination of the 360 MHZ 1H NMR data (in CDCl3 and in C6D6) and the Cotton effects of ORD spectra of its saturated lactone and cyclopentanone derivatives, we considered that britanin must be ambros-11(13)-en-2β, 4β, 6α, 8α-tetraol-12-oic-(12,8)- lactone, 2, 6-diacetate (7). Since the large values for J6,7, J7,8, J8,9, J9,10 and J1,10 indicate the existence of successive a-a trans coupling in all vicinal protons form C6 to C1, the cofnformation of the cycloheptane ring must be in chair from. The other constitutent isolated from the same plant has been identified as taraxasteryl palmitate.     

Indirect spectrophotometric determination of gentamicin and vancomycin antibiotics based on their oxidation by potassium permanganate

Four simple, accurate, sensitive and economical procedures (A–D) for the estimation of gentamicin sulphate and vancomycin hydrochloride, both in pure form and in pharmaceutical formulations have been developed. The methods are based on the oxidation of the studied drugs by a known excess of potassium permanganate in sulphuric acid medium and subsequent determination of unreacted oxidant by reacting it with amaranth dye (method A), acid orange II (method B), indigocarmine (method C) and methylene blue (method D), in the same acid medium at a suitable λ_max=521, 485, 610 and 664 nm, respectively. The reacted oxidant corresponds to the drug content. Regression analysis of Beer-Lambert plots showed good correlations in the concentration ranges 4–8, 3–8, 4–9 and 5–9 μg ml⁻¹ with gentamicin and 4–8, 1.5–4, 1.5–4 and 3.5–5.5 μg ml⁻¹ with vancomycin for methods A, B, C, and D, respectively. The molar absorptivity, sandell sensitivity, detection and quantification limits were calculated. The stoichiometric ratios for the cited drugs were studied. The optimum reaction conditions and other analytical parameters were evaluated. The influence of the substance commonly employed as excipients with these drugs were studied. The proposed methods were applied to the determination of these drugs in pharmaceutical formulations. The results have demonstrated that the methods are equally accurate and reproducible as the official methods.     

Sulfonated carbon materials with hydrophilic and lipophilic properties

Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for the etherification of isopentene with methanol to produce tert amyl methyl ether （TAME） in toluene solution （lipophilic system）. Microcalorimetric adsorptions of water and benzene showed that the HS-C was highly hydrophilic without the lipophilicity, while the H-PRC exhibited both the hydrophilicity and lipophilicity. Thus, the HS-C was well dispersed in aqueous solution and difficult to separate from it. On the other hand, the H-PRC was highly active, more active than the acidic resin （D008） and sulfuric acid, for the synthesis of DMM in aqueous solution. The H-PRC was also highly active, more active than the HS-C, for the etherification of isopentene with methanol to produce TAME in toluene solution, probably owing to its amphiphilic surface property as well as its strong surface acidity as measured by the microcalorirnetric adsorption of NH3.     

Synthesis of Glutamic Acid-based Cluster Galactosides and Their Binding Affinities with Liver Cells

Structurally well defined di-, tri- and tetra-valent cluster galactosides were synthesized in a convenient way.Oligo-glutamic acids were assembled as scaffolds. The presence of amine groups in these three ligands is expected to couple with drugs or genes for delivery. The binding affinities of these cluster galactoses to liver cells were determined by in vitro binding studies. Among them, the tetravalent cluster galactose (19) showed the highest affinity to liver cell. It is therefore a promising targeting device for the specific delivery of drugs or genes to parenchymal liver cells.     

Development of LC–MS method for analysis of paclitaxel-inhibited growth and enhanced therapeutic response in human glioblastoma cells

Glioma stem cells are considered responsible for drug resistance and glioma relapse resulting in poor prognosis in glioblastoma multiforme. SU3 glioma cell is a highly invasive glioma stem cell line from the patients with glioblastoma multifrome. It is of great significance to study the efficacy and molecular mechanism for anticancer drug effects on SU3 glioma cells. In this work, we develop a liquid chromatography–mass spectrometry(LC–MS) method for direct analysis of the role of drugs(paclitaxel)on SU3 glioma cells at the molecular level. We use the specific fluorescence dyes to evaluate cell viability,the levels of ROS and GSH when the cells were treated with drugs. In addition, the LC–MS platform was successfully employed to detect the amount of 6-O-methylguanine, demonstrating that it is effective to induce cell apoptosis and enhance the cytotoxic response of SU3 glioma cells. The analytical linear equals are Y = 9.49 ? 105 X + 2.42 ? 104 for 6-O-methylguanine(R2= 0.9998) and Y = 4.72 ? 104 X + 2.21 ? 103(R2= 0.9996) for 7-methylguanine. Thus, the combination of cell-specific fluorescence dyes and LC–MS method enables us to reveal the molecular mechanism of paclitaxel-inhibited growth and enhanced therapeutic response in the chemotherapy for glioma multiforme.     

Traceless Synthesis of Hydantoin by Focused Microwave Irradiation

Hydantoin analogs have shown versatile therapeutic applications and some of them have been approved by FDA as drugs. For example, Fosphenytoin as a sodium channel antagonist is used for the treatment of epilepsy. Phenytoin has antiarrhythmic, anticonvulsant and antineuralgic activities. Ethotoin and Mephenytoin both show anticonvulsant effect. Nilutamide is a non-steroidal orally-active antiandrogen in combination with surgical castration for the treatment of stage D2 metastatic prostate c…     

Application of PCA and HCA to the Structure-activity Relationship （SAR） Study of Fluoroquinolones

1 INTRODUCTION The earliest antibacterial agents used as chemo- therapeutic drugs in the 1920s were synthetic agents, such as sulponamides. Since the discovery of peni- cillin and its entry into clinical use in the 1940s, the field has been dominated over the past 50 years by natural products or their semi-synthetic derivatives. The fluoroquinolones are the only synthetic anti- bacterial agents to rival β-lactams for impact in clinical usage in the antibacterial field. In recent years, …     

Procedure for the analysis of sedative drugs with the use of an array of piezoelectric sensors (Exemplified in the determination of the drug Corvalol)

A procedure was developed for the headspace analysis of sedative drugs with the use of a quartz piezoelectric microbalance array. The effects of the nature of film coatings in piezoelectric cell electrodes on the working weight range and the sorption properties of sorbent films were found. An array of six piezoelectric sensors with different response functions in the vapors of the drug Corvalol and its highly volatile constituents was proposed. The procedure is suitable for the quality assessment of other pharmaceuticals based on ethyl alcohol and natural peppermint oil. Original Russian Text ￠ T.A. Kuchmenko, A.V. Kozhukhova, Yu.I. Orobinskii, 2008, published in Zhurnal Analiticheskoi Khimii, 2008, Vol. 63, No. 3, pp. 314–321.     

Synthesis and Crystal Structure of a Dinuclear Cu(II) Complex with Tridentate Schiff Base and Azido Bridge

1 INTRODUCTION The azido ligand is an efficient superexchange path-way for propagating magnetic interaction between theparamagnetic centers, such as copper(II), giving di-nuclear, tetranuclear, 1D, 2D and 3D complexes[1～4].The versatility of this ligand due to its diverse bin-ding modes leads to the variation in magnetic pro-perties that depend on its orientation with respect tothe magnetic centers. In general, the bridging modesobserved for the azido group are endtoend and en-don. In…