Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

UV-C辐照降解水中磺胺类药物

采用C类紫外线或称为短波紫外线（即UV-C）辐照降解水中磺胺类药物,考察了磺胺类药物种类、UV光强、磺胺类药物初始浓度、反应液pH对降解效果的影响。结果表明UV-C辐照对磺胺嘧啶、磺胺甲基嘧啶和磺胺甲恶唑的降解过程均符合拟一级反应动力学。UV-C辐照技术对磺胺甲恶唑的去除率最高,在反应液pH为7,光强为142μW/cm^2,初始浓度为0.02mmol/L条件下,辐照30 min后磺胺甲恶唑去除率达到67.80%,而磺胺嘧啶和磺胺甲基嘧啶去除率仅15%左右。通过增大紫外光强和减小初始浓度,可提高反应速率和磺胺甲恶唑去除率。反应液pH对反应效果的影响显著,酸性条件更利于UV-C辐照降解磺胺甲恶唑。     

高效液相色谱-在线柱后衍生荧光检测法同时测定水产品中14种磺胺类药物残留

建立水产品中14种磺胺类药物的高效液相色谱-柱后衍生荧光检测法。均质后的水产品试样用乙酸乙酯提取、盐酸溶液反萃取、正己烷脱脂、反相色谱柱分离、在线柱后衍生、荧光检测器检测、内标法定量。14种磺胺类药物(磺胺、磺胺嘧啶、磺胺噻唑、磺胺甲基嘧啶、磺胺5-甲氧嘧啶、磺胺二甲基嘧啶、磺胺甲氧哒嗪、磺胺氯哒嗪、磺胺6-甲氧嘧啶、磺胺甲基异噁唑、磺胺多辛、磺胺异噁唑、磺胺二甲氧哒嗪、磺胺喹噁啉)的线性范围为2.5～800μg/L,线性相关系数均大于0.9934;在2.5～200μg/kg三个添加水平范围内的平均回收率为88.9%～98.6%,相对标准偏差均小于6.96%。14种磺胺类药物的定量检出限为2.5～20μg/kg。方法重现性好、灵敏度高,杂质干扰少,广泛适用于水产品中磺胺类药物残留的检测。     

液相色谱-串联质谱法检测蜂蜜中15种喹诺酮类和17种磺胺类药物残留

目的建立同时测定蜂蜜中15种喹诺酮和17种磺胺类药物残留的液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,HPLC-MS/MS)检测方法。方法样品经过磷酸盐缓冲溶液(pH=8)提取,过HLB(hydrophile-lipophile balance)固相萃取柱净化。以CORTECS C18色谱柱(2.1 mm×100 mm,1.6μm)分离,以5 mmol乙酸铵、0.1%甲酸水(A)和0.1%甲酸-乙腈(B)作为流动相进行梯度洗脱。质谱分析以电喷雾为离子源(electrospray ionization,ESI+),采用多反应监测(multiple reaction monitoring,MRM)。结果本方法在15 min内完成32种目标化合物的分离。15种喹诺酮和17种磺胺类药物在1.0、5.0和10.0μg/kg添加水平的回收率为54.9%~122.5%,相对标准偏差(relative standard deviation,RSD)小于18.7%(n=6),方法检出限为0.4μg/kg,定量限为1.0μg/kg。结论该方法快速、准确、灵敏,适合测定蜂蜜中喹诺酮和磺胺类药物残留。     

DART-Orbitrap质谱法快速筛查饲料中磺胺类药物

利用新型离子化技术--实时直接分析(DART)离子源与高分辨质谱Orbitrap联用,建立饲料中非法添加磺胺类药物的快速筛查方法。通过对DART离子化温度、样品检测模式等参数进行探索优化,最终确定饲料经过乙腈-水溶液简单提取,液体筛网模块进样,450 ℃下离子化,Orbitrap高分辨质谱在全扫描模式下定性检测,并进行相关的方法学验证,方法检出限为1.0~4.0 μg/g。该方法前处理简单、检测速度快、定性准确、样品通量大、环保无污染,能满足饲料中非法添加磺胺类药物快速筛查的要求。     

N-取代磺酰胺类化合物的合成研究进展

N-取代磺酰胺类化合物在制药行业是非常重要的一类化合物,因其表现出了广泛的生物活性,如抗癌、抗炎和抗病毒等生理功能,备受研究者们的关注。本文从不同的底物出发概述了N-取代磺酰胺类化合物的合成方法。     

Preparation of quality control materials for the determination of sulfonamides in animal feed

A feasibility study of the preparation of quality control materials for the analysis of medicated feeds has been carried out. Two analytical methodologies for the analysis of sulfonamides in feeds were developed, validated and applied to homogeneity and stability studies. Pig feeds spiked with sulfadiazine and sulfadimidine were prepared. The drugs were spiked at 500 µg g^?1, representing what can be expected in a commercial medicated feed, and at 2 and 5 µg g^?1, which roughly correspond to drug-free feeds cross-contaminated during the fabrication process. The homogeneity of both the bulk and the bottled materials was verified. A stability study of the materials containing 2 and 5 µg g^?1 of sulfonamides was carried out over an 18-month period at room temperature, at 4°C and ?20°C. The determination of sulfadiazine and sulfadimidine in samples coming from these homogeneity and stability studies of the quality control materials was carried out by high-performance liquid chromatography (HPLC) with either ultraviolet light or fluorimetric detection, depending on the concentration of the analytes in the samples.     

基质固相分散-高压液相色谱-高分辨质谱法测定猪肉中22种磺胺类药物的残留

目的 建立基质固相分散-高压液相色谱-高分辨质谱测定猪肉中22种磺胺类药物残留量的测定方法, 包括磺胺苯酰、磺胺醋酰、磺胺氯哒嗪、磺胺嘧啶、磺胺间二甲氧嘧啶、磺胺二甲嘧啶、磺胺甲基嘧啶、磺胺多辛、磺胺间甲氧嘧啶、磺胺甲氧哒嗪、磺胺对甲氧嘧啶、磺胺甲噁唑、磺胺甲噻二唑、磺胺二甲噁唑、磺胺苯吡唑、磺胺吡啶、磺胺喹噁啉、磺胺噻唑、磺胺异噁唑、磺胺胍、甲氧苄啶、磺胺索嘧啶。方法 猪肉样品与弗罗里硅土混合, 研磨均匀, 装入空的固相萃取管中, 用15 mL 1%乙酸二氯甲烷: 乙酸乙酯(1∶3, v/v)洗脱, 洗脱液用氮气吹干, 残渣用1 mL乙腈: 10 mmol/L乙酸铵溶液(15∶85, v/v)溶解。加入1 mL正己烷混合离心, 取下层溶液, 经0.22 μm滤膜过滤后用Agilent Poroshell 120 EC-C18(2.1 mm×150 mm, 2.7 μm)色谱柱分离, 高分辨质谱测定。结果 22种磺胺类药物在 10~100 μg/kg范围内线性关系良好, 相关系数r>0.99, 除磺胺甲噻二唑、甲氧苄啶和磺胺脒/磺胺胍加标回收率小于40%外, 其余均大于60%, 定量限为 5~10 μg/kg。结论 本方法具有前处理快速、高效、有机试剂用量少、成本小等优点, 适用于猪肉中磺胺类药物残留量的测定。     

A New Mechanism of the Selective Photodegradation of Antibiotics in the Catalytic System Containing TiO2 and the Inorganic Cations

The mechanism of sulfisoxazole (SFF) selective removal by photocatalysis in the presence of titanium (IV) oxide (TiO₂) and iron (III) chloride (FeCl₃) was explained and the kinetics and degradation pathways of SFF and other antibiotics were compared. The effects of selected inorganic ions, oxygen conditions, pH, sorption processes and formation of coordination compounds on the photocatalytic process in the presence of TiO₂ were also determined. The Fe³⁺ compounds added to the irradiated sulfonamide (SN) solution underwent surface sorption on TiO₂ particles and act as acceptors of excited electrons. Most likely, the SFF degradation is also intensified by organic radicals or cation organic radicals. These radicals can be initially generated by reaction with electron holes, hydroxyl radicals and as a result of electron transfer mediated by iron ions and then participate in propagation processes. The high sensitivity of SFF to decomposition caused by organic radicals is associated with the steric effect and the high bond polarity of the amide substituent.