Dihydropyrimidones based chloride ion chemosensor functional in aqueous solution under environmentally relevant conditions

Compounds 1 and 2 were synthesised using multi-component one-pot condensation reaction between 2-hydroxynaphthaldehyde, urea/thiourea and ethyl/methyl acetoacetate, catalysed with Zn(ClO₄)₂·6H₂O in methanol. Compounds 1 and 2 were purified and characterised using ¹H and ¹³C NMR, mass and CHN analyses. Organic nanoparticles (ONPs) were developed from compounds 1 and 2 using reprecipitation technique. Size and morphology of nano-aggregates N1 and N2 were analysed using DLS and transmission electron microscope techniques. Nano-aggregates of 1 and 2 were further subjected to chemosensory applications in aqueous medium. Efficient nano-aggregates of compound 1 have shown excellent detection limit of 0.04 nM for chloride in aqueous medium. None of the other anions tested caused any interference in the detection of chloride. However, nano-aggregates of compound N2 were not active for any particular ion in aqueous medium. The difference in the recognition properties can be due to the difference in the size and electronegativity of oxygen and sulfur moieties attached on 1 and 2, respectively. The sensor was used to determine the chloride content in tap water. Results were validated using existing methods and the performance of the N1 was found to be in a satisfactory error range.     

In search of dark horses: Affinity maturation of phage-displayed ligands

Summary Most combinatorial libraries are sparse in that only a tiny fraction of the relevant class of compounds is represented. This sparseness can be compensated in some measure by alternating rounds of selection with rounds of mutagenesis. Thus, clones are selected from the initial library by some criterion of fitness, such as affinity for a particular receptor. The selected clones are then mutagenized to generate a mutant library, which serves as input to the next round of selection, and so on. If the first round of selection is too stringent, rejecting all but the very fittest clone in the initial library (the initial champion), we might miss dark horses; clones in the initial library that are inferior to the initial champion, yet can be mutated to even higher fitness than can that champion. A more thoughtful strategy is to alternate nonstringent selection with simultaneous mutagenesis of many selected clones en masse.     

1,1-二(2-苯并咪唑基)-2-苯基乙烯衍生物荧光受体的合成与阳离子识别

合成了3种新型1,1-二(2-苯并咪唑基)-2-苯基乙烯衍生物——1,1-二(2-苯并咪唑基)-2(4-氰基苯基)乙烯(1)、1,1-二(2-苯并咪唑基)-2(4-甲氧羰基苯基)乙烯(2)和1,1-二(2-苯并咪唑基)-4-苯基-1,3-丁二烯(3),通过核磁共振氢谱和碳谱(1H、13C NMR)、质谱(MS)对它们进行了结构表征。用紫外可见吸收光谱(UV-V is)和荧光发射光谱测定了该阳离子受体与不同金属离子(Zn2 、Cd2 、Hg2 和Cu2 )的络合选择性。结果表明:该荧光受体对Zn2 、Cd2 、Hg2 和Cu2 均具有较高的选择性和荧光响应。     

Rutin induces endoplasmic reticulum stress-associated apoptosis in human triple-negative breast carcinoma MDA-MB-231 cells – In vitro and in silico docking studies

Rutin is a bioactive compound that possesses anti-tumor activities through triggering apoptosis. Triple-negative breast cancer (TNBC) is insensitive to targeted anti-tumoral drugs, and drug resistance in TNBC poses a challenge for a successful cure. The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. This study aimed to find potential ER stress targets in triple-negative breast cancer. The viability of cells was evaluated using an MTT assay. Cell migration and proliferation were done by wound scratch and colony formation assay. Cell cycle detection, measurement of ER stress, mitochondrial membrane potential disruption, and cell death identification was performed using flow cytometry. The interaction of rutin with ER stress proteins is predicted using in silico docking. The pattern of gene expression was determined by qRT-PCR. The elevated rate of cell viability, cell cycle arrest, ER stress, MMP, and apoptotic induction was observed in combination treatment. Rutin exhibited the highest glide score with ASK1 and JNK. The results of qRT-PCR showed that rutin induced apoptosis through upregulation of ASK1 and JNK. The present study provides strong evidence supporting an important role of the ER stress response in mediating rutin-induced apoptosis in triple-negative breast cancer.     

A selective ATP chromogenic sensor for use in an indicator displacement assay

We synthesized a dinuclear Zn²⁺ complex that is useful as a sensor for ATP in a DMSO/H₂O (1:9, v/v) solvent system via a simple indicator displacement assay (IDA). This chromogenic sensor method can be used to analyze 0.1-2.0 μM of ATP with no interference from ADP or AMP.     

傅里叶变换红外光谱研究鲤鱼雌激素受体与邻苯二甲酸酯的相互作用

通过电泳结合电洗脱(SDS-PAGE)的方法分离纯化鲤鱼体内的雌激素受体,得到高纯度的受体;再通过傅里叶变换红外光谱探讨雌激素受体与邻苯二甲酸二正丁酯(DBP)结合后其结构的变化,通过实验发现,配体DBP能与雌激素受体结合并对雌激素受体的结构产生了明显的影响。     

Dioxin-Type Activity for Polyhalogenated Arylic Derivatives. A QSAR Model Based on MTD-Method

Abstract

QSARs by the Minimal Steric/Topologic Difference (MTD)-method were performed for general toxicity, hepatic cytosol receptor binding and aryl hydrocarbon hydroxylase induction on polychlorinated and polybrominated derivatives of dibenzo-p-dioxin, dibenzofuran and biphenyl. Low energy conformations selected by molecular mechanics calculations and superpositions of the considered structures for the construction of the hypermolecule were performed using the COSMIC molecular modelling package. The multiconformational-MTD-method was used. Correlation coefficients of r = 0.8 to 0.9 were obtained as well as good cross-validation results, for series of up to 70 compounds. Conformational analysis of flexible molecules suggests their accommodation in the receptor site also in non planar conformations corresponding to the first stable one (minimum energy costs) above the global minimum. A common optimised receptor site can be attributed for all series of compounds, with a rather high symmetry, which suggests that these compounds produce gene activation by dimerization of their receptor protein. The high toxicity of dioxin-type compounds could be explained by their high stability that produce long lasting, abnormally high levels of some detoxification enzymes—without toxic effects at their low and normal levels.     

Androgen receptor binding affinity of pesticide "active" formulation ingredients. QSAR evaluation by COREPA method

The COREPA approach for identifying the COmmon REactivity PAttern of biologically similar chemicals was employed to upgrade the recently derived affinity pattern for high androgen receptor (AR) binding affinity. The training set consisted of 28 steroidal and nonsteroidal ligands whose AR binding affinity was determined in competitive binding assays (in terms of p K i ). The interatomic distances between nucleophilic sites and their charges providing distinct and non-overlapping integral patterns for active and inactive chemicals were assumed that it was related with the endpoint, which was under study. These stereoelectronic characteristics were used to predict p K i values of pesticide "active" formulation ingredients in an attempt to identify chemicals with potential AR binding affinity.     

A facile and regioselective synthesis of rimonabant through an enamine-directed 1,3-dipolar cycloaddition

Rimonabant is a high-potency cannabinoid type-1 (CB₁) receptor inverse agonist that has recently been approved in the European Union as a treatment for obesity. Current methods of synthesis require several steps that have long reaction times and/or lack regioselectivity. Here we present a novel, regioselective synthesis of rimonabant though an enamine-directed 1,3-dipolar cycloaddition. In addition, we present a new and more reactive hydrazonoyl halide for the generation of the requisite nitrile imine dipole.