Rapid Electrochemical Detection of Propranolol and Metoprolol in Pharmaceutical Preparations Using Stabilized Lipid Films

This work reports a technique for the rapid electrochemical detection of propranolol and metoprolol in pharmaceutical preparations using stabilized lipid films. Microporous filters composed of glass fibers (nominal pore sizes 0.7 and 1.0 μm) were used as supports for the formation and stabilization of these devices. The lipid film is formed on the filter by polymerization prior to its use. This stabilized after storage in air. Lipid films composed of phosphatidylcholine were used for the detection of propranolol and metoprolol in pharmaceutical preparations. The stabilized lipid membranes provided artificial ion gating events in the form of transient signals within about 60 and 34 s after exposure of the membranes to propranolol and metoprolol, respectively. The magnitude of the transient current signal was related to the concentration of propranolol and metoprolol in bulk solution in the micromolar range. The mechanism of signal generation was investigated by differential scanning calorimetric studies. These studies revealed that the adsorption of the drug is through the hydrophobic aryl terminal of the compound, whereas the hydrophilic groups were directed towards the electrolyte solution. This adsorption caused a rapid alteration of the electrochemical double layer of the lipid film (i.e., capacitance changes) that resulted in the transient ion current signal. The present technique was used for the rapid detection of propranolol and metoprolol in pharmaceutical preparations and can function for repetitive uses after storage in air. Future research is targeted to the determination of these chemicals in human biofluids such as urine of athletes.     

Bia-amperometric quantification of salbutamol in pharmaceutical products

This paper presents a simple, rapid and reproducible method of analysis of salbutamol in pharmaceutical products, utilizing batch injection analysis (BIA) associated with amperometric detection. A study of salbutamol oxidation demonstrated a strong dependence between electrode fouling and pH. All determinations were done utilizing a glassy carbon electrode in presence of 3.0 mol l⁻¹ NaOH. A large linear dynamic range from 8×10⁻⁷ to 2×10⁻⁴ mol l⁻¹ was obtained by using an injected volume of 100 μl with a detection limit of 2.5×10⁻⁷ mol l⁻¹. R.S.D. of 0.92% for 50 successive injections of 4×10⁻⁶ mol l⁻¹ of salbutamol and a sample throughput of 60 samples per hour were achieved. The method was applied for salbutamol quantification in syrups.     

Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users’ local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps—which run calculations “in the cloud” rather than on users’ local computers—browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.     

关联规则增量式更新的改进算法

关联规则是数据挖掘中的重要研究内容之一，对在事务数据库不变，只对最小支持度和最小可信度进行改变的情况下，针对关联规则的维护问题，设计了一个增量式更新的改进算法AIUA。     

基于关联规则和技术功效矩阵的企业技术创新机会发现和辅助决策方法

为助力科技型创新企业准确且快速地从外部捕获创新技术机会, 提出一种企业技术机会发现和辅助决策方法. 首先, 挖掘领域内的技术热点、技术重点和有潜力的技术作为领域技术创新机会. 然后, 通过关联规则分析领域技术机会和企业已有技术之间的相关性, 进一步结合技术掌握度和新颖度, 识别更适合企业的技术创新机会. 最后, 创新性地采用Sen-BERT语言模型和K-means聚类方法构建技术功效矩阵, 辅助企业从功能需求的角度进行技术创新决策. 以电动汽车领域为例验证了该方法的可行性.     

7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1

Inhibitors of epigenetic writers such as DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug and probe discovery. To advance epigenetic probes and drug discovery, chemical companies are developing focused libraries for epigenetic targets. Based on a knowledge-based approach, herein we report the identification of two quinazoline-based derivatives identified in focused libraries with sub-micromolar inhibition of DNMT1 (30 and 81 nM), more potent than S-adenosylhomocysteine. Also, both compounds had a low micromolar affinity of DNMT3A and did not inhibit DNMT3B. The enzymatic inhibitory activity of DNMT1 and DNMT3A was rationalized with molecular modeling. The quinazolines reported in this work are known to have low cell toxicity and be potent inhibitors of the epigenetic target G9a. Therefore, the quinazoline-based compounds presented are attractive not only as novel potent inhibitors of DNMTs but also as dual and selective epigenetic agents targeting two families of epigenetic writers.     

Reverse fragment based drug discovery approach via simple estimation of fragment contributions

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Determination of nicotinamide by stopped-flow injection method in pharmaceutical formulations

A simple stopped-flow injection system with spectrophotometric detection was proposed for the determination of nicotinamide (NAM) in pharmaceutical formulations. In this system cyanogen chloride formed from the combination of an acidic KSCN with the NaClO streams reacts with injected NAM to form glutaconic aldehyde. Then the product of these three components was coupled with another buffered (pH 3.5) stream of barbituric acid and directed towards the detector. A 45 s after sample injection the pump was stopped for 130 s. During this time the reactants in the flow cell were provided with the required temperature (40 °C) by placing the cell in a home made cell jacket to increase the yield of the polymethine dye product. Eventually, the absorbance of the formed pink color dye was monitored spectrophotometrically at 560 nm and NAM in the concentration range of 1.0–25.0 μg/mL (R = 0.9974 and D.L = 0.5 μg/mL) was determined. The results obtained by this method were compared statistically and agree with those obtained by the method described in the British Pharmacopoeia.     

Determination of Total Chromium in Biological Samples by Automated Reagent Injection Chemiluminescence Analysis

A sensitive method for the determination of total chromium in real samples by flow injection–chemiluminescence (FI–CL) analysis was proposed. It was found that the CL intensity from luminol–lysozyme reaction could be markedly quenched, and the decrease of CL intensity was linear with the logarithm of Cr(III) concentrations over the range of 5.0 to 4000 pg mL^?1 with a detection limit of 2.0 pg mL^?1 (3σ) and relative standard deviations (RSDs) of 3.0, 2.6, and 2.0% for 10, 100, and 1000 pg mL^?1 Cr(III) (n = 7), respectively. At a flow rate of 2.0 mL min^?1, the whole process including sampling and washing could be accomplished within 36 s. The proposed CL method was successfully applied to the determination of total chromium in pharmaceutical capsules, a dietary supplement, and spiked human serum samples, with recoveries from 92.2 to 108.4% and RSDs of less than 4.0%. Using the homemade FI–CL model, the binding constant (K = 4.38 × 10⁶ L mol^?1) and the binding sites (n ≈ 1) of Cr(III) to lysozyme were given.     

Flexizyme‐Mediated Genetic Reprogramming As a Tool for Noncanonical Peptide Synthesis and Drug Discovery

Noncanonical peptides occur frequently in Nature, and often display high bioactivity. However, the lack of tractable systems for the synthesis of diverse libraries of such peptides has thus far hampered their development as drugs. Genetic reprogramming techniques, in which noncanonical amino acids may be incorporated into peptides, have largely removed this limitation. This Concept article outlines the development of these techniques with an emphasis on drug discovery.