生、炒决明子中无机元素的分析测定

为测定生决明子中无机元素水平,探讨其药效物质基础及炒制对其含量的影响,采用原子荧光法和等离子发射光谱法等测定了不同产地、批次的生、炒决明子中重金属及微量元素的含量。结果表明,不同产地的生、炒决明子含有的重金属元素均没有超过食品卫生标准。决明子经过炮制后,无机元素变化情况:硫、钠、铬、钡、锂、镍、锶等元素炮制前后变化不大;钙、钾、镁、锰、锌有益元素的含量略有增高;汞、铅、砷有害元素的含量略有下降。可见决明子饮片药用是安全的,炒制工艺对决明子无机元素含量有一定影响,其特有无机元素的种类和含量对揭示决明子药效的物质基础具有意义。     

肝素在生长因子控制释放中的应用*

典型的抗凝血药物肝素作为硫酸化的多糖在体内具有多重生物活性,而这些生物活性是通过与生长因子和细胞因子等蛋白质的相互作用来发挥的。由于它与肝素亲和性生长因子具有特异的糖胺聚糖-蛋白质相互作用,近年来被广泛地应用于生长因子的控制释放中,以达到稳定负载于载体材料特别是水凝胶载体中的生长因子并保持其生物活性、延缓释放的作用。本文介绍了近年来肝素在组织工程用生长因子控制释放系统中应用研究的最新进展。     

单乙酰大花旋覆花内酯衍生物研究

合成;生理活性;单乙酰大花旋覆花内酯衍生物研究     

A Multiwell-Based Assay for Screening Thyroid Hormone Signaling Disruptors Using thibz Expression as a Sensitive Endpoint in Xenopus laevis

There is a need for rapidly screening thyroid hormone (TH) signaling disruptors in vivo considering the essential role of TH signaling in vertebrates. We aimed to establish a rapid in vivo screening assay using Xenopus laevis based on the T3-induced Xenopus metamorphosis assay we established previously, as well as the Xenopus Eleutheroembryonic Thyroid Assay (XETA). Stage 48 tadpoles were treated with a series of concentrations of T3 in 6-well plates for 24 h and the expression of six TH-response genes was analyzed for choosing a proper T3 concentration. Next, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA), two known TH signaling disruptors, were tested for determining the most sensitive TH-response gene, followed by the detection of several suspected TH signaling disruptors. We determined 1 nM as the induction concentration of T3 and thibz expression as the sensitive endpoint for detecting TH signaling disruptors given its highest response to T3, BPA, and TBBPA. And we identified betamipron as a TH signaling agonist, and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) as a TH signaling antagonist. Overall, we developed a multiwell-based assay for rapidly screening TH signaling disruptors using thibz expression as a sensitive endpoint in X. laevis.     

Structural Refinement of 2,4-Thiazolidinedione Derivatives as New Anticancer Agents Able to Modulate the BAG3 Protein

The multidomain BAG3 protein is a member of the BAG (Bcl-2-associated athanogene) family of co-chaperones, involved in a wide range of protein–protein interactions crucial for many key cellular pathways, including autophagy, cytoskeletal dynamics, and apoptosis. Basal expression of BAG3 is elevated in several tumor cell lines, where it promotes cell survival signaling and apoptosis resistance through the interaction with many protein partners. In addition, its role as a key player of several hallmarks of cancer, such as metastasis, angiogenesis, autophagy activation, and apoptosis inhibition, has been established. Due to its involvement in malignant transformation, BAG3 has emerged as a potential and effective biological target to control multiple cancer-related signaling pathways. Recently, by using a multidisciplinary approach we reported the first synthetic BAG3 modulator interfering with its BAG domain (BD), based on a 2,4-thiazolidinedione scaffold and endowed with significant anti-proliferative activity. Here, a further in silico-driven selection of a 2,4-thiazolidinedione-based compound was performed. Thanks to a straightforward synthesis, relevant binding affinity for the BAG3BD domain, and attractive biological activities, this novel generation of compounds is of great interest for the development of further BAG3 binders, as well as for the elucidation of the biological roles of this protein in tumors. Specifically, we found compound 6 as a new BAG3 modulator with a relevant antiproliferative effect on two different cancer cell lines (IC₅₀: A375 = 19.36 μM; HeLa = 18.67 μM).     

Design,Synthesis, Molecular Docking,and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-phenylimidazolidin-4-one and 2-aminothiazol-4-one Derivatives

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1–11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.     

Bioactivity of Two Polyphenols Quercetin and Fisetin against Human Gastric Adenocarcinoma AGS Cells as Affected by Two Coexisting Proteins

It is recognized that minor dietary components polyphenols have anticancer effects on digestive tract, lung, leukemia, and other cancers, while polyphenols also can covalently or noncovalently interact with major dietary components proteins such as casein, soybean proteins, whey proteins, and bovine serum albumin. Thus, whether the noncovalent interaction between the molecules of two polyphenols (quercetin and fisetin) and two proteins (bovine serum albumin and casein) has positive or negative impact on anticancer activities of the polyphenols against human gastric adenocarcinoma AGS cells was assessed in this study. The two polyphenols had obvious anticancer activities to the cells, because dose levels as low as 20–160 μmol/L caused reduced cell viability of 30.0–69.4% (quercetin) and 24.6–63.1% (fisetin) (using a cell treatment time of 24 h), or 9.9–48.6% (quercetin) and 6.4–29.9% (fisetin) (using a cell treatment time of 48 h). However, the cell treatments by the polyphenols in the presence of the two proteins mostly caused lower polyphenol activity toward the cells, compared with those treatments by the polyphenols in the absence of the proteins. Specifically, the presence of the proteins led to reduced growth inhibition in the cells, because higher cell viability of 33.2–86.7% (quercetin) and 29.1–77.7% (fisetin) at 24 h, or 14.1–66.8% (quercetin) and 7.9–59.0% (fisetin) at 48 h, were measured in these treated cells. The two coexisting proteins also yielded the polyphenol-treated cells with less mitochondrial membrane potential loss, less formation of reactive oxygen species, and decreased cell apoptosis. Thus, it is highlighted that the noncovalent interaction between dietary polyphenols and proteins resulted in weakened anticancer ability for the polyphenols to the gastric cancer cells.     

Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD

Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.     

Synthesis of 4,5-Dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione Derivatives and Their Application as Protein Kinase Inhibitors

This study represents the design and synthesis of a new set of hybrid and chimeric derivatives of 4,5-dihydro-4,4-dimethyl-1H-[1,2]dithiolo[3,4-c]quinoline-1-thiones, the structure of which the tricyclic fragment linearly bound or/and condensed with another heterocyclic fragment. Using the PASS Online software, among the previously synthesized and new derivatives of 1,2-dithiolo[3,4-c]quinoline-1-thione we identified 12 substances with pleiotropic activity, including chemoprotective and antitumor activity. All the synthesized derivatives were screened for their inhibitory assessment against a number of kinases. Compounds which exhibited prominent inhibition percentage in cells (>85%) were also examined for their inhibitory efficiency on human kinases via ELISA utilizing sorafenib as a reference standard to estimate their IC₅₀ values. It was revealed that compounds 2a, 2b, 2c, and 2q displayed a significant inhibition JAK3 (IC₅₀ = 0.36 μM, 0.38 μM, 0.41 μM, and 0.46 μM, respectively); moreover, compounds 2a and 2b displayed excellent activities against NPM1-ALK (IC₅₀ = 0.54 μM, 0.25 μM, respectively), against cRAF[Y340D][Y341D], compound 2c showed excellent activity, and compound 2q showed weak activity (IC₅₀ = 0.78 μM, 5.34 μM, respectively) (sorafenib IC₅₀ = 0.78 μM, 0.43 μM, 1.95 μM, respectively). Thus, new promising preferred structures for the creation of drugs for the treatment of cancer and other multifactorial diseases in the future have been found.     

光子晶体生化传感器的构建及应用

光子晶体生化传感分析是基于光子晶体的结构特性将生化信号放大或转换为光电可读信号,并通过仪器或肉眼进行定量或半定量分析的方法.本文围绕着光子晶体生化传感器的材料选择与构建、传感机理、设计及应用三方面进行综述.在材料选择与构建上,本文从单分散胶体颗粒、电磁复合胶体颗粒、纳米线、金属-有机框架等方面进行综述;在传感机理上,本...