BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

Expression of Opioid Receptors in Cells of the Immune System

The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.     

Treating Arterial Ageing in Patients with Diabetes: From Mechanisms to Effective Drugs

Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.     

中国与日本兽药残留限量标准比较分析研究

目的研究我国与日本兽药残留限量标准的异同。方法根据中华人民共和国国农业部第235号公告以及日本肯定列表、厚生劳动省第370号公告,比较两国法律法规涉及的禁用与限量物质清单在兽药种类、残留食品种类、残留限量指标值等方面的异同。结果我国兽药残留限量标准涉及123种兽药、3大类食品、12种动物与9种靶组织、550个限量指标,日本则涉及243种兽药、4大类食品、16种动物与8种靶组织、3705个限量指标。两者相比,我国83种兽药与日本相同, 445个限量指标与日本810个限量指标具有可比性。在中日标准涉及的具有可比性的限量指标中,我国有215个指标与日本等同,有80个指标比日本严格,有139个指标比日本宽松。结论在兽药残留限量标准涉及的可比指标值方面,我国二分之一的指标值与日本对应指标值是等同的。     

液相色谱-串联质谱法测定保健食品中非法添加的18种镇静催眠类药物

目的建立液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry, UPLC-MS/MS)测定保健食品中非法添加的18种镇静催眠类药物的分析方法。方法样品经甲醇超声提取,采用C18(2.1mm×50 mm, 1.8μm)色谱柱, 0.1%甲酸水溶液-甲醇为流动相,梯度洗脱,流速0.3 mL/min;质谱检测器为ESI源(正离子)多反应监测模式进行定性、定量检测。结果 18种被测组分在5～100 ng/mL浓度范围内线性关系良好,相关系数均大于0.999。5、20、50ng/mL3种添加浓度的平均回收率在77.6%～98.5%之间,相对标准偏差为1.1%～5.5%。方法学检出限均低于0.2μg/g。结论该方法专属性强、灵敏度高、操作简便、测定快速,可用于保健食品中非法添加的18种镇静催眠类药物的质量监控。     

QuEChERS结合高效液相色谱-串联质谱法同时测定黄颡鱼中7种染料类兽药残留

目的建立黄颡鱼中孔雀石绿、隐色孔雀石绿、结晶紫、隐色结晶紫、亚甲基蓝、天青A、天青B残留量检测的QuEChERS-高效液相色谱-串联质谱(high performanc eliquid chromatography-tandem mass spectrometry, HPLC-MS/MS)联用方法。方法样品中加入乙腈于-18℃冷冻30 min,再加入去水剂无水硫酸镁和氯化钠,漩涡振荡离心后取上清液加入净化萃取试剂,漩涡离心后氮气吹至近干,乙腈复溶并注入HPLC-MS/MS测试。结果在最优的条件下, 7种染料类兽药在0.1～10 ng/mL范围内线性关系良好,方法平均回收率为78.2%～95.3%,精密度为3.0%～5.6%。结论该方法简单、快速、可靠,线性关系良好,检出限低,灵敏度高,可用于黄颡鱼中7种染料类兽药残留测定。     

Sulfonylguanidine Derivatives as Potential Antimelanoma Agents

Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified.     

保健食品中非法添加药物事件及检测技术

近年来,向保健品中非法添加药物的现象时有发生。本研究针对不同保健食品的类别,梳理近年来发生的保健食品非法添加药物事件,对各类保健食品中常可能非法添加的药物及危害进行总结,并且对不同类别的保健食品中非法添加药物的检测技术进行归纳,分析技术的优缺点,为保健食品的市场监管提供参考。     

抗生素类药物的研究进展

抗生素是由微生物或高等动植物在生活史中所产生的能干扰细胞发育功能,具有抑菌或杀菌作用的化合物。近年来,抗生素在人类和动物疾病以及农业中的大量使用,使得抗生素耐药危机爆发,导致曾经容易治疗的疾病变得再次致命。因此,开发新型有效的抗生素迫在眉睫。当前,越来越多的科研工作者开始从细胞生物学方面入手,研究抗生素在微生物中的作用机理,以求发现细菌耐药的根本原因。本文综述了抗生素的研发历史及作用机制,基因组学在抗生素研发中的重要作用,抗生素复配组合使用及构建化学品库实现老药新用,并展望了抗生素类药物未来的发展方向。     

Gold Drugs with {Au(PPh3)}+ Moiety: Advantages and Medicinal Applications

Following the success of Auranofin as an anti-arthritic drug, search for novel gold drugs has afforded a large number of [L−Au(PPh₃)] complexes that exhibit notable salutary effects. Unlike Au(III)-containing species, these gold complexes with {Au(PPh₃)}⁺ moiety are stable in biological media and readily exchange L with S- and Se-containing enzymes or proteins. Such exchange leads to rapid reduction of microbial loads or induction of apoptotic cell death at malignant sites. In many cases the lipophilic {Au(PPh₃)}⁺ moiety delivers a desirable toxic L to the specific cellular target in addition to exhibiting its own beneficial activity. Further research and utilization of this synthon in drug design could lead to novel chemotherapeutics for treatment of drug-resistant pathogens and cancers.