Simple and sensitive electrochemical sensing of amethopterin by using carbon nanobowl/cyclodextrin electrode.

Resulted from the severe side effects, the development of inexpensive, simple and sensitive method for amethopterin (ATP, an antineoplastic drug) is very important but it still remains a challenge. In this work, low cost nanohybrid composed of carbon nanobowl (CNB) and ß-cyclodextrins (ß-CD) (CNB-CD) was prepared with a simple autopolymerization way and applied as electrode material to develop a novel electrochemical sensor of ATP. Scanning-/transmission-electron microscopy, Fourier transform infrared spectrum, photographic image and electrochemical technologies were utilized to characterize morphologies and structure of the as-prepared CNB and CNB-CD materials. On the basic of the coordination advantages from CNB (prominent electrical property and surface area) and ß-CD (superior molecule-recognition and solubility capabilities), the CNB-CD nanohybrid modified electrode exhibits superior sensing performances toward ATP, and a low detection limit of 0.002 µM coupled with larger linearity of 0.005-12.0 µM are obtained. In addition, the as-prepared sensor offers desirable repeatability, stability, selectivity and practical application property, confirming that this proposal may have important applications in the determination of ATP.

Efficient Synthesis and Biological Evaluation of 6-Trifluoroethoxy Functionalized Pteridine Derivatives as EGFR Inhibitors.

BACKGROUND: Pteridine-based scaffolds have been widely prevalent in pharmaceuticals, such as kinase inhibitors targeting EGFR, FLT3 and PI3K/mTOR which are attractive targets for the anticancer therapy. OBJECTIVE: This work aimed at designing and synthesizing 6-2,2,2-trifluoroethoxy functionalized pteridine-based derivatives for investigation of their anti-cancer activities as EGFR inhibitor. METHODS: Pteridine-based derivatives were synthesized in 6 steps involving amination, bromination, cyclization, alkoxylation, chlorination and coupling reactions. Cellular anti-proliferative activities and inhibition activities on EGFR signaling of these pteridine derivatives in vitro were determined by the MTT assay and western blot analysis, respectively. Molecular docking simulation studies were carried out by the crystallographic structure of the erlotinib/EGFR kinase domain [Protein Data Bank (PDB) code: 1M17]. RESULTS: The compound 7m, with IC50 values of 27.40 µM on A549 cell line, exhibited comparable anti-proliferative activity relative to the positive control. Besides, western blots showed its obvious down-regulation of p-EGFR and p-ERK expression at 0.8 µM. The molecular docking model displayed a hydrogen bond between Met-769 amide nitrogen and N-1 in pteridine motif of 7m which lied at the ATP binding site of EGFR kinase domain. CONCLUSION: The inhibition of 7m on cellular growth was comparable to that of the positive control. The inhibitory activities of 7m on EGFR phosphorylation and ERK phosphorylation in A549 cell line were relatively superior to that of the positive control. Both results suggested that the antiproliferative activity of 7m against A549 cell line was caused by inhibition of EGFR signaling pathway, providing a new perspective for the modification of pteridine-based derivatives as EGFR inhibitor.

Electrochemiluminescent immunoassay for the lung cancer biomarker CYFRA21-1 using MoOx quantum dots.

Molybdenum oxide quantum dots (MoOx QDs) were synthesized by a one-pot method and used as a versatile probe in an electrochemiluminescent (ECL) immunoassay of the non-small cell lung cancer biomarker cytokeratin 19 fragment 21-1 (CYFRA21-1) as a model analyte. The MoOx QDs exhibited stable and strong cathodic green ECL, with an emission peak at 535 nm, in the presence of K2S2O8 within the potential range of -2.0 to 0 V. On exposure to CYFRA21-1, the ECL decreases because of the immunoreaction between CYFRA21-1 and its antibody which generates a barrier for electron transfer. The determination of CYFRA21-1 with favorable analytical performances was successfully realized under the optimal conditions. ECL decreases linearly in the 1 pg mL-1 to 350 ng mL-1 CYFRA21-1 concentration range, and the detection is as low as 0.3 pg mL-1. Excellent recoveries from CYFRA21-1-spiked human serum indicate that the assay can be operated under physiological conditions. Graphical abstractSchematic representation of the fabrication of molybdenum oxide quantum dots (MoOx QDs) and the electrochemiluminescent (ECL) immunoassay based on the use of the MoOx QDs ECL probe for cytokeratin 19 fragment 21-1 (CYFRA21-1).

Poly[dibromidobis[µ-1-(pyridin-4-ylmeth-yl)-1H-1,2,4-triazole-κN:N']cadmium].

The title coordination polymer, [CdBr(2)(C(8)H(8)N(4))(2)](n), arose from a layer-separated diffusion synthesis at room temperature. The title compound is isotypic with the I and Cl analogues. The Cd atom, located on an inversion center, is coordinated by two bromide ions and four N atoms (two from triazole rings and two from pyridyl rings) in a distorted trans-CdBr(2)N(4) octa-hedral arrangement. The bridging 1-(4-pyridyl-meth-yl)-1H-1,2,4-triazole ligands are twisted [dihedral angle between the triazole and pyridine rings = 72.56 (13)°], affording a two-dimensional 4(4) sheet structure in the crystal.

A two-dimensional manganese(II) complex: poly[bis-(µ(2)-4,4'-bipyrid-yl)tetra-kis-(µ(2)-3,5-dinitro-benzoato)dimanganese(II)].

The Mn atom in the title compound, [Mn(2)(C(7)H(3)N(2)O(6))(4)(C(10)H(8)N(2))(2)](n), is six-coordinated by two N atoms and four O atoms, forming a distorted octa-hedral geometry. The Mn-O bond lengths are in the range 2.1281 (13)-2.2011 (12) Šand the Mn-N bond lengths are 2.269 (2) and 2.278 (2) Å. Mn(II) atoms are double-bridged along the a axis by two pairs of bi-monodentate carboxyl groups, forming a double-stranded chain, while the bidentate 4,4'-bipyridine ligand bridges the Mn atom along the b axis. This results in a two-dimensional structure constructed of oblong grids with the sides of length 11.634 and 5.075 Å

Poly[dichloridobis[µ-1-(4-pyridyl-meth-yl)-1,2,4-triazole]cadmium(II)].

In the title coordination polymer, [CdCl(2)(C(8)H(8)N(4))(2)](n), the Cd(II) atom, lying on an inversion center, is coordinated by two Cl atoms and two triazole N atoms and two pyridyl N atoms from four 1-(4-pyridyl-meth-yl)-1,2,4-triazole (pmta) ligands in a distorted trans-CdCl(2)N(4) octa-hedral arrangement. The bridg-ing pmta ligands, with a dihedral angle between the triazole and pyridyl rings of 71.86 (8)°, link the Cd atoms into a 4(4) sheet parallel to (02). π-π inter-actions between the triazole rings [centroid-centroid distance = 3.428 (2) Å] connect the sheets.

Poly[dichloridobis[µ-1-(4-pyridylmeth-yl)-1H-1,2,4-triazole]copper(II)].

The title coordination polymer, [CuCl(2)(C(8)H(8)N(4))(2)](n), arose from a layer-separated diffusion synthesis at room temperature. The Cu atom (site symmetry ) is coordinated by two chloride ions and four N atoms (two from triazole rings and two from pyridyl rings) in a distorted trans-CuCl(2)N(4) octa-hedral arrangement. The bridging 1-(4-pyridylmeth-yl)-1H-1,2,4-triazole ligands [dihedral angle between the triazole and pyridine rings = 68.08 (8)°] result in a two-dimensional 4(4) sheet structure in the crystal.

Novel biodegradable blend matrices for controlled drug release.

Phosphorylcholine-functionalized poly-epsilon-caprolactone (PC-PCL) is a new biodegradable polymer with good biocompatibility. In this study modulation of the controlled release of Ibuprofen (IB), a model drug, from poly-epsilon-caprolactone (PCL) by direct blending with PC-PCL is investigated. The influence of several factors such as the content of PC-PCL in the blend, drug loading and the molecular weight of PCL matrix upon the IB release is recognized. The release mechanism is discussed in terms of degradation/erosion profiles and hydrophilicity of the blend matrices. The IB release rate increased with the PC-PCL content because PC-PCL increased the hydrophilicity and biodegradability of the blends. Simultaneously, that release rate decreased with increase in the molecular weight of PCL in the blend. The drug loading in the blend also affected the release property of the matrix. Analysis of the release profiles following the power law indicated that the IB release was governed mainly by diffusion kinetics.

Structure and release behavior of PMMA/silica composite drug delivery system.

The preparation, characterization, and in vitro release of aspirin from polymethylmethacrylate (PMMA)/silica composites prepared via a sol-gel route are reported. The in vitro drug release test revealed that the release rate of aspirin in PBS increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilyl) propyl methacrylate (MSMA), a coupling agent, decreased the drug release rate. The drug release rate/composite structure relationship was studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and swelling ratio (SR) measurement. The results indicated that the interface between polymer matrix and inorganic fillers has significant influence on the drug release behavior of the composite materials. In addition, models of mass transfer based on Fickian diffusion law at constant temperature and pressure were employed to analyze the results of the in vitro drug release experiments. The drug release behaviors of the composite samples fitted well with the Fickian diffusion model. The values of k, which is in direct proportion to drug release rate, increased with the increasing content of silica while decreased with that of MSMA in the composite samples.