New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum avicennae: Effects on Neutrophil Pro-Inflammatory Responses

Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4–18). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory concentration (IC₅₀) values ≤7.65 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤8.17 µg/mL. This investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.     

咪达那新的合成研究进展

对咪达那新的合成方法进行了归纳和比较,重点介绍了关键中间体4-(2-甲基-1-咪唑基)-2,2-二苯基丁腈的合成及由关键中间体合成咪达那新的研究进展,为咪达那新的进一步研究及工业化生产提供参考。     

UPLC-MS/MS法同时测定减肥食品中55种非法添加物

目的 建立超高效液相色谱-串联质谱同时测定减肥类食品中55种非法添加物的分析方法。方法 样品经甲醇超声提取后,采用Agilent Eclipse Plus C₁₈ RRHD色谱柱(2.1 mm×100 mm,1.8μm)分离,以乙腈-0.1%甲酸为流动相进行梯度洗脱。在正负离子扫描条件下,采用动态多反应监测模式监测。结果 55种非法添加药物在相应的线性范围内均呈现良好线性关系,相关系数大于0.995,平均回收率75.2%～121.6%,相对标准偏差<12%,各化学药物的检测限在0.02～1.25μg/g。应用该方法对50批样品进行了检测,其中有38批次样品检出托拉塞米、大黄素、西布曲明、N-单去甲基西布曲明、N,N-双去甲基西布曲明、比沙可啶、麻黄碱、甲基麻黄碱、氢氯噻嗪、氟西汀等非法添加物。结论 该方法简单、快速、灵敏、准确、高效,兼具定性定量检测的优点,可用于食品中减肥类化学药物的高通量检测。     

Existing Drugs Considered as Promising in COVID-19 Therapy

COVID-19 is a respiratory disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease at first was identified in the city of Wuhan, China in December 2019. Being a human infectious disease, it causes high fever, cough, breathing problems. In some cases it can be fatal, especially in people with comorbidities like heart or kidney problems and diabetes. The current COVID-19 treatment is based on symptomatic therapy, so finding an appropriate drug against COVID-19 remains an immediate and crucial target for the global scientific community. Two main processes are thought to be responsible for the COVID-19 pathogenesis. In the early stages of infection, disease is determined mainly by virus replication. In the later stages of infection, by an excessive immune/inflammatory response, leading to tissue damage. Therefore, the main treatment options are antiviral and immunomodulatory/anti-inflammatory agents. Many clinical trials have been conducted concerning the use of various drugs in COVID-19 therapy, and many are still ongoing. The majority of trials examine drug reposition (repurposing), which seems to be a good and effective option. Many drugs have been repurposed in COVID-19 therapy including remdesivir, favipiravir, tocilizumab and baricitinib. The aim of this review is to highlight (based on existing and accessible clinical evidence on ongoing trials) the current and available promising drugs for COVID-19 and outline their characteristics.     

TCDCANa的合成及抗菌抗炎作用研究

以鹅去氧胆酸(CDCA)和牛磺酸为基本原料合成了牛磺鹅去氧胆酸钠(TCDCANa),以萃取和重结晶法提纯,收率63.4%,w(TCDCANa)≥92%,以TLC和IR法确定了其结构。并将牛磺鹅去氧胆酸钠与鹅去氧胆酸钠(CDCANa)进行了抗菌、抗炎和镇咳对比实验。药效实验结果为:TCDCANa和CDCANa均具有抗革兰阳性菌作用(抑菌环直径分别为2.46±0.08cm和1.91±0.13cm),抗炎作用抑制率分别为(79.1±25.4)%和(71.2±23.1)%,镇咳作用减咳率分别为(29.1±5.6)%和(18.2±6.8)%,牛磺鹅去氧胆酸钠与鹅去氧胆酸钠间存在显著性差异。药效实验表明,TCDCANa具明显的镇咳、平喘和抗菌作用,其作用强于CDCANa。     

An acryl resin-based swellable microneedles for controlled release intradermal delivery of granisetron

Swellable microneedles (SMNs) are made of hydrogels and can deliver drug with controlled delivery rate by the cross-link density of the hydrogel. In this study, an acryl resin-based SMNs was developed for poorly water-soluble drugs. The making process of the SMNs is very simple and only need 60?min. The SMNs has high mechanical strength and is not easily broken. In-vitro release of SMNs-loaded model drug, granisetron base (GRB), was investigated. The results showed that seven days controlled release of GRB was obtained when SMNs contained pore-foaming agents (1.5% dicalcium phosphate (CaHPO₄) and 1.5% polyvinylpyrrolidone (PVP)). The maximum amount delivered into skin was 86.158?±?7.82% of the initial GRB (2.1?mg) loaded on SMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma GRB concentrations and that the controlled release of 2.1?mg dose was observed for 144?hours. In conclusion, these SMNs provided a potential minimally invasive route for controlled-release systemic delivery of poorly water-soluble drugs.     

Combined structural and biological activities for new polyunsaturated fatty derivatives obtained by biotechnological process

The objective of this study is to demonstrate the use of new polyunsaturated fatty derivatives for cutaneous applications. These new compounds present an analogue structure of cutaneous lipid, stabilize the polyunsaturated fatty acids (face to oxidation) and demonstrate specific biological activities. Three molecules described are Omega 6 fatty acid stabilized compound (O6FASC), the O3FASC and the O9FASC. The derivatives are synthesized via the same biotechnological process. This work describes the choice of final structure, the design of the biotechnological process and the free solvent enzymatic synthesis used for the synthesis of these three cutaneous lipid analogues. The restructuring effect of such analogues has been demonstrated with an in vivo study on volunteers. The stabilization of the O3FASC and O6FASC, and the biological activities of these three compounds are presented. The O6FASC shows very good results in anti-inflammatory effects; the O3FASC has anti-stress activities, whereas the O9FASC presents interesting results in improving elasticity and firmness. All these activity tests are presented in this work.     

Investigating the chlorination of acidic pharmaceuticals and by-product formation aided by an experimental design methodology

The degradation of seven acidic drugs and two metabolites during chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). A triple-quadrupole (QqQ) system was used to follow the time course of the pharmaceuticals and by-products, while a quadrupole time-of-flight (Q-TOF) system was also used for the identification of the by-products. Under strong chlorination conditions (10 mg/L Cl₂, 24 h), only four of the target compounds were significantly degraded: salicylic acid, naproxen, diclofenac and indomethacine. The degradation kinetics of these four compounds were investigated at different concentrations of chlorine, bromide and pH by means of a Box-Behnken experimental design. Depending on these factors, measured pseudo-first order half-lives were in the ranges: 23-573 h for salicylic acid, 13-446 min for naproxen, 5-328 min for diclofenac and 0.4-13.4 min for indomethacine. Also, it was observed that chlorine concentration was the overall most significant factor, followed by the bromide concentration (except for indomethacine), resulting in increased degradation kinetics as they are increased. The degradation path of salicylic acid, naproxen and diclofenac consisted of aromatic substitution of one or two hydrogens by chlorine and/or bromide. Moreover, for diclofenac, two other by-products corresponding to a decarboxylation/hydroxylation pathway from the monohalogenated products were also identified. On the other hand, indomethacine degradation did not lead to halogenation products but to oxidation ones. The investigation of these by-products in real samples by LC-MS/MS (QqQ) showed that the halogenated derivates of salicylic acid occurred in all the drinking water and wastewater samples analysed.