Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

This review updates and follows‐up a previous review by highlighting recent advancements regarding capillary electromigration methodologies and applications in pharmaceutical analysis. General approaches such as quality by design as well as sample injection methods and detection sensitivity are discussed. The separation and analysis of drug‐related substances, chiral CE, and chiral CE‐MS in addition to the determination of physicochemical constants are addressed. The advantages of applying affinity capillary electrophoresis in studying receptor–ligand interactions are highlighted. Finally, current aspects related to the analysis of biopharmaceuticals are reviewed. The present review covers the literature between January 2013 and December 2015.     

Paeonenoides D and E: Two New Nortriterpenoids from Paeonia lactiflora and Their Inhibitory Activities on NO Production

Two new nortriterpenoids, paeonenoides D and E ( 1 and 2 , resp.), together with seven known compounds, were isolated from the roots of Paeonia lactiflora. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1 – 7 were screened for inhibitory effects against NO production in LPS‐induced RAW246.7 macrophages and for cytotoxic activities against HL‐60, Hep‐G2, and SK‐OV‐3 cell lines. Compounds 1 – 3 and 5 – 7 exhibited inhibitory activities with IC₅₀ values in the range of 9.6–32.2 μM . Triterpenoids with an epoxide ring and a free COOH function, 1 – 3 , showed effectively increased activities compared with other pentacyclic triterpenoids. Compounds 1 – 6 showed significant cytotoxic activities against the Hep‐G2 cell line and modest cytotoxic activities against HL‐60 and SK‐OV‐3 cell lines.     

Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.     

Three New Lycopodium Alkaloids from Phlegmariurus fargesii

Three new Lycopodium alkaloids, fargesiines A – C ( 1  –  3 , resp.), along with a known compound ( 4 ), were isolated from the whole plants of Phlegmariurus fargesii. Their structures were elucidated on the basis of spectroscopic data and chemical correlations. Compounds 1  –  4 were tested in an assay for acetylcholinesterase (AChE) inhibitory activity.     

Anti‐Inflammatory Activity of a Novel Acetylene Isolated from the Roots of Angelica tenuissima Nakai

Three polyacetylenes, one novel and two known, were isolated from the root of Angelica tenuissima. Using ¹H‐ and ¹³C‐NMR, COSY, HMBC, and HMQC, their structures were found to be (3R,8S)‐heptadeca‐1‐en‐4,6‐diyne‐3,8‐diol ( 1 ), falcarindiol ( 2 ), and oplopandiol ( 3 ). Absolute configurations of compound 1 were established using Mosher's esterification. In addition, the polyacetylenes ( 1 – 3 ) were evaluated for their anti‐inflammatory activity. Compounds 1 and 3 showed potent inhibitory activity against lipopolysaccharide‐induced nitric oxide (NO) production in RAW267.7 macrophage cells with IC₅₀ values of 4.31 and 5.06 μm, respectively. Compound 1 strongly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)‐2 in a concentration‐dependent manner.     

A Novel C22 Terpenoid from the Cultured Perovskia atriplicifolia

A novel terpenoid, named perovskiaol ( 1 ), was isolated from the cultured Perovskia atriplicifolia. Its structure was elucidated by comprehensive spectroscopic analysis as well as by quantum chemical computation of electronic circular dichroism spectra. Perovskiaol ( 1 ) was a novel C₂₂ terpenoid containing a unique D‐ring simultaneously fused with rings A, B, and C, and encountered in nature for the first time. Cytotoxic bioassay suggested perovskiaol ( 1 ) possessed significant cytotoxic activity inhibiting NB4, A549, and HepG 2 cell lines with IC₅₀ values of 2.35, 1.47, and 0.81 μm , respectively.     

Isocassiaoccidentalin B,A New C‐Glycosyl Flavone Containing a 3‐Keto Sugar,and Other Constituents from Cassia nomame

A new C‐glycosyl flavone containing a 3‐keto sugar, isocassiaoccidentalin B ( 1 ), was isolated from whole Cassia nomame (Sieber ) Honda plants, along with eleven known compounds, including two flavonoids ( 2 and 3 ), five flavonoid glycosides ( 4  –  8 ), two chalcones ( 9 and 10 ), and two phenylpropanoids ( 11 and 12 ). The chemical structures of all compounds were determined via 1D‐ and 2D‐NMR, and ESI‐MS. Among these, compounds 2 , 3 , 7 , and 8 were found to be the most potent in inhibiting nitric oxide release. Compounds 1 , 2 , 4 , 8 , 9 , and 10 showed significant free‐radical scavenging activity.     

Electrochemical Investigations of Mn and Al Co‐doped Li2FeSiO4/C Cathodes for Li‐Ion Battery

Few studies on orthosilicate cathodes co‐doped with two cations have been reported until now. Here, we report the synthesis of Mn and Al co‐doped Li₂Fe_0.8?xMn_0.2Al_xSiO₄ (x = 0.05 and 0.1) by a solid‐state reaction route and characterized by X‐ray diffraction (XRD), particle size analysis, scanning electron microscopy (SEM), galvanostatic charge/discharge tests, and capacity intermittent titration technique (CITT), as compared to the single‐doped Li₂Fe_0.8Mn_0.2SiO₄. Though the co‐doping leads to a slight decreased capacity owing to the increased impurity and Al³⁺ inertia, a better cycling performance is obtained as expected. Especially when x is 0.05, the modified sample (Li₂Fe_0.75Mn_0.2Al_0.05SiO₄) shows an initial discharge capacity of 159.3 mAh/g and high capacity retention of 78% after 50 charge/discharge cycles. The present work indicates that a synergistic effect of Mn and Al co‐substitution at the Fe site could partly make up the disadvantage of single Mn doping, and might provide an effective guide for the dopant incorporation to Li₂FeSiO₄ systems.     

Environment‐sensitive Fluorescent Turn‐on Chemical Probe for the Specific Detection of O‐Methylguanine‐DNA Methyltransferase (MGMT) in Living Cells

MGMT protein, which has been associated with resistance to antitumor alkylation drugs for many patients, is a very useful prognostic marker to provide a guide for therapeutic decisions. Considering the large number of cellular samples that have to be handled daily at the hospitals, it is thus important to develop a rapid and simple analytical method to distinguish MGMT activity in different types of cells. In this paper, we describe a MGMT‐activated fluorescence turn‐on probe for the rapid no‐wash imaging of MGMT in living cells. The probe consists of a specific MGMT suicide pseudosubstrate, O⁶‐benzyl‐guanine and an environment‐sensitive fluorophore, SBD. In the presence of MGMT, the enzyme transfers SBD to the protein active site where the hydrophobic surrounding causes the fluorophore to exhibit more than 50‐fold fluorescence enhancement. With this probe, bright fluorescence was observed for MGMT‐positive, Hela S3 and MCF‐7 cells, while MGMT‐deficient CHO cells displayed no fluorescence. We believe that this fluorescence activation probe design can also be extended to detect other transferases, for which there are still no effective methods to image them in living cells.     

Synthesis and Characterization of Copper(II)–Phosphonate Coordination Chain Array of Metallocages

Reaction of CuCl₂ ·2H₂O and 2,4,6‐tris(phosphorylmethyl)mesitylene (H₆tpmm) in H₂O?DMF solution at room temperature afforded green crystals of [Cu₆(H₂tpmm)₃(H₂O)₉]·3H₂O ( 1 ), which were characterized by Fourier transform infrared (FT‐IR), thermogravimetric (TG) analysis, and powder X‐ray diffraction (PXRD). The solid‐state structure of 1 reveals a one‐dimensional chain array of M₄L₂ ‐metallocages constituted by the connection of two kinds of metallocage units, namely MC‐A (phosphonate/water‐bridged) and MC‐B (phosphonate‐bridged only), via μ₂‐O(phosphonate)? Cu bonds in ABAABA order. The tris‐phosphonate ligand H₆tpmm is partially deprotonated to form H₂tpmm^4?, which displays a cis,cis,cis conformation to bridge six Cu(II) centers via two monodentate phosphonate groups in a η ⁰:η ⁰:η ¹‐bonding mode and one tridentate phosphonate group in a μ₄, η ¹:η ¹:η ²‐bondingng mode.