含膦酸酯结构单元的磺胺衍生物合成与抗菌活性

为了寻找抗菌候选化合物,采用基于片段的药物发现方法,以氨基膦酸酯和磺酰氯为原料,设计合成了15个含膦酸酯结构单元的磺胺衍生物,经IR、1HNMR和13CNMR确认结构。采用两倍稀释法测定目标化合物的MIC(最小抑菌浓度)。结果表明:部分目标化合物呈潜在的抗菌活性,对所测试标准菌和耐药菌均有抑制活性。其中,化合物Ⅱf〔N-[(二乙氧基膦酰基)-4-氟苯甲基]-4-甲氧基苯磺酰胺〕对金黄色葡萄球菌(S. aureus)、大肠埃希菌(E. coli)、耐甲氧西林金黄色葡萄球菌(MRSA)及耐氟喹诺酮类大肠杆菌(MREC)的MIC分别为32、64、128和128μg/mL,化合物Ⅱl〔N-[(二乙氧基膦酰基)-4-氟苯甲基]-4-氟苯磺酰胺〕对S. aureus、E. coli、MRSA及MREC的MIC分别为32、32、64和64μg/mL,抗菌活性优于对照药磺胺嘧啶。     

3-<i>epi</i>-bufotalin suppresses the proliferation in colorectal cancer cells through the inhibition of the JAK1/STAT3 signaling pathway

Traditional Chinese medicine (TCM) has been increasingly employed in the last decades in China for both preventing and treating a variety of cancers. 3-epi-bufotalin is an active ingredient of TCM “Chanpi” with anti-tumor potential. However, the effect and mechanism of 3-epi-bufotalin on colorectal cancers were not well disclosed. The present study demonstrated that 3-epi-bufotalin could reduce viability, trigger apoptosis, and block the cell cycle at the G₂/M stage in colorectal cancer cell lines HT29, RKO, and COLO205 in vitro. Moreover, 3-epi-bufotalin inhibited the JAK1/STAT3 signaling pathway. These results indicated the anti-proliferation ability of 3-epi-bufotalin in colorectal cancer cells.     

A novel fluorescent covalent organic framework for the selective detection of fluoride ion

Journal of Materials Science - A novel fluorescent covalent organic framework containing trimethyl silicon group (COF-TMS) was designed and prepared via the Povarov reaction to be used to detect...     

四氢小檗碱衍生物的合成与表征

文章根据文献中具有降血糖作用的四氢黄连碱型季铵化合物的构效关系,合成了一系列N-7位带有酰胺侧链的四氢小檗碱类衍生物,所得目标产物均经IR、1H NMR和ESI-MS确认。     

我校药剂学开放性实验教学改革探索

开放性实验是一种以学生为主体的教学模式,在药剂学实验中实施开放性实验教学适用于我校药学类各相关专业,具有因材施教,充分调动学生的积极性,培养学生独立思考、主动创新的能力等多方面优点。本文介绍了我校实行药剂学开放性实验教学的必要性和具体的改革措施,期望通过开放性实验教学改革进一步提高我校药剂学实验的教学效果。     

Silver nanowire–graphene hybrid nanocomposites as label for sensitive electrochemical immunoassay of alpha-fetoprotein

A facile and sensitive mediator-free electrochemical immunoassay was developed for determination of alpha-fetoprotein (AFP) in human serum with a sandwich-type mode by using silver nanowire–graphene hybrid nanocomposites (AgNW–GPs) as label. One-pot hydrothermal method was used for the synthesis of the AgNW–GPs with the aid of trisodium citrate. The as-prepared AgNW–GP was not only utilized for the label of horseradish peroxidase-conjugated anti-AFP (HRP-anti-AFP) with highly loading capacity, but also displayed good electrochemical behaviors. Compared with the conventional HRP-anti-AFP-based electrochemical immunoassay, the sensitivity of the proposed immunoassay by using the synthesized nanolabels was greatly improved. Under optimal conditions, the electrochemical immunosensor exhibited a wide linear range of 0.05–400 ng/mL with a low detection limit (LOD) of 5 pg/mL AFP (at 3s_B). Intra- and inter-assay coefficients of variation were below 10% and 8.5%, respectively. The selectivity and stability of the immunosensor were acceptable. In addition, the methodology was also validated by assaying 16 positive serum samples and 7 negative serum samples, receiving a good correlation with the results obtained from the referenced electrochemiluminescence method.     

Applying linear interaction energy method for binding affinity calculations of podophyllotoxin analogues with tubulin using continuum solvent model and prediction of cytotoxic activity

Podophyllotoxin and its analogues have important therapeutic value in the treatment of cancer, due to their ability to induce apoptosis in cancer cells in a proliferation-independent manner. These ligands bind to colchicine binding site of tubulin near the α- and β-tubulin interface and interfere with tubulin polymerization. The binding free energies of podophyllotoxin-based inhibitors of tubulin were computed using a linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model. A training set of 76 podophyllotoxin analogues was used to build a binding affinity model for estimating the free energy of binding for 36 inhibitors (test set) with diverse structural modifications. The average root mean square error (RMSE) between the experimental and predicted binding free energy values was 0.56 kcal/mol which is comparable to the level of accuracy achieved by the most accurate methods, such as free energy perturbation (FEP) or thermodynamic integration (TI). The squared correlation coefficient between experimental and SGB–LIE estimates for the free energy for the test set compounds is also significant (R² = 0.733). On the basis of the analysis of the binding energy, we propose that the three-dimensional conformation of the A, B, C and D rings is important for interaction with tubulin. On the basis of this insight, 12 analogues of varying ring modification were taken, tested with LIE methodology and then validated with their experimental potencies of tubulin polymerization inhibition. Low levels of RMSE for the majority of inhibitors establish the structure-based LIE method as an efficient tool for generating more potent and specific inhibitors of tubulin by testing rationally designed lead compounds based on podophyllotoxin derivatization.     

High performance carbon nanotube spun yarns from a crosslinked network

We report a new method to create covalent crosslinks between carbon nanotubes (CNTs) with reduced intertube and interbundle spaces, for improving the mechanical properties of CNT spun yarns. This is achieved through the pretreatment of a CNT yarn with 4-carboxybenzenediazonium tetrafluoroborate to form reactive carboxyphenyl groups on the CNT sidewalls. These carboxyphenyl groups are then reacted with a multifunctional crosslinker hexa(methoxymethyl) melamine, leading to a highly crosslinked network within the yarn. The CNT yarns were characterized by X-ray photoelectron spectroscopy, focused ion beam scanning electron microscope, and also assessed for their mechanical properties. The results showed that the method developed effectively improved mechanical properties of CNT yarns: we are able to produce CNT yarns with a tensile strength up to 2.5 GPa and Young’s modulus 121 GPa.     

Unprecedented oxidative properties of mesoporous silica materials: Towards microwave-assisted oxidation of lignin model compounds

The unusual oxidative ability of mesoporous silicas towards oxidation of an important lignin model molecule, 1,2-(4-hydroxy-3methoxy-phenoxy) ethanol, apocynol under microwave irradiation is presented in this work. Mesoporous MCM-41, HMS, SBA-15 and amorphous silica were employed as catalysts in the present study. Different reactivities were obtained for the various silica materials. It was assumed that the substrate conversion and product selectivity were highly influenced by the nature of mesoporous silica materials. Based on the nature of the catalysts and reaction product profile, a plausible mechanism has been proposed.