Eburnamine derivatives and the brain

The Apocynaceae plant family contains a great number of so called eburnamine-vincamine alkaloids. Quite a few of these alkaloids exert varied pharmacological activities on the cell multiplication, cardiovascular system, and brain functions. Many derivatives were also synthesized to find pharmacologically active compounds better characterized and safer to be administered than the natural plant alkaloids themselves. We concentrate on the eburnamine structures with cerebral activities in this review. Vincamine, vinburnine, vindeburnol, apovincaminate, and vinpocetine (cis-ethyl-apovincaminate) all share modulatory effects on brain circulation and neuronal homeostasis, bear antihypoxic and neuroprotective potencies to various degrees. The most eminent compound of this class of alkaloids is vinpocetine. Since its introduction to the market as a neuroprotective agent many non clinical and clinical studies proved vinpocetine's effects on calmodulin dependent phosphodiesterase E1, on sodium, calcium channels, peripheral benzodiazepine receptor, and glutamate receptors as well as its clinical usefulness in the treatment of post-ischaemic stroke disease states and various disorders of cerebrovascular origin. Lately, positron emission tomography studies proved that vinpocetine has a rapid uptake in the primate and human brain with a heterogeneous distribution pattern (preference areas: thalamus, basal ganglia, and visual cortex) both after intravenous and oral administration. Vinpocetine exerts beneficial effects in cerebral glucose metabolism and regional cerebral blood flow in chronic post-stroke patients.     

氟喹诺酮类抗菌药物对2554株细菌的抗菌活性分析

目的:监测我国不同地区13所医院34个研究病房患者中分离的细菌对氟喹诺酮抗菌药物的耐药状况。方法:于2000年7月1目至2001年6月30日收集13所医院分离的2 554株病原菌,采用国际标准的二倍稀释法进行体外敏感试验,并按美国国家临床实验标准委员会(NCLLS)2001版标准,判断菌株对抗菌药物的敏感度,并计算出所测细菌对抗菌药物的耐药率(R％)、中介率(I％)和敏感率(S％)。结果:共收集到2 554株致病菌,包括革兰阳性菌958株(37.5％)和革兰阴性菌1596株(62.5％);氟喹诺酮抗菌药物中的新品种——莫西沙星和加替沙星对大多数革兰阳性球菌的作用明显强于环丙沙星和氧氟沙星(P<0.05),对革兰阴性肠杆菌科细菌的作用也较强;而非发酵革兰阴性菌中的铜绿假单胞菌和不动杆菌属对左氧氟沙星的耐药率最低。结论:新一代氟喹诺酮抗菌药物莫西沙星和加替沙星对革兰阳性球菌的作用增强,对革兰阴性肠杆科细菌的作用无减弱;杜绝不合理滥用,是防止细菌对氟喹诺酮药物耐药的最有效方法。     

Synthesis and antitumor activities of sinomenine derivatives on rings A and C

A series of new sinomenine derivatives were designed, synthesized, and evaluated in tumor inhibitory activity, such as human triple negative breast cancer cell line (MDA-MB-231), glioma cell line (A172), human lung cancer cell line (A549), human colon cancer cell line (HCT-8). The modifications were carried out on rings A and C of the sinomenine by esterificating on phenolic hydroxyl with good yields. The highlight of this work was that the synthetic procedures were concise and sinomenine derivatives demonstrated promising antitumor activities.     

青藤碱结构改造的研究进展

青藤碱是一种来源于防己科植物青风藤中的生物碱,在结构上属于异喹啉类,具有多种生物活性。在临床上主要用于治疗风湿性及类风湿性关节炎和心律失常等疾病。但由于其用药剂量大、对光/热不稳定、体内代谢快、易引起过敏反应,科研人员一直致力于对青藤碱进行结构修饰,以期开发出高效、低毒的青藤碱衍生物。对近年来青藤碱的结构修饰研究进展做一综述。     

Design,synthesis, and biological evaluation of novel 1,2‐diaryl‐4‐substituted‐benzylidene‐5(4H)‐imidazolone derivatives as cytotoxic agents and COX‐2/LOX inhibitors

A new series of 1,2‐diaryl‐4‐substituted‐benzylidene‐5(4H)‐imidazolone derivatives 4a–l was synthesized. Their structures were confirmed by different spectroscopic techniques (IR, ¹H NMR, DEPT‐Q NMR, and mass spectroscopy) and elemental analyses. Their cytotoxic activities in vitro were evaluated against breast, ovarian, and liver cancer cell lines and also normal human skin fibroblasts. Cyclooxygenase (COX)‐1, COX‐2 and lipoxygenase (LOX) inhibitory activities were measured. The synthesized compounds showed selectivity toward COX‐2 rather than COX‐1, and the IC₅₀ values (0.25–1.7 µM) were lower than that of indomethacin (IC₅₀ = 9.47 µM) and somewhat higher than that of celecoxib (IC₅₀ = 0.071 µM). The selectivity index for COX‐2 of the oxazole derivative 4e (SI = 3.67) was nearly equal to that of celecoxib (SI = 3.66). For the LOX inhibitory activity, the new compounds showed IC₅₀ values of 0.02–74.03 µM, while the IC₅₀ of the reference zileuton was 0.83 µM. The most active compound 4c (4‐chlorobenzoxazole derivative) was found to have dual COX‐2/LOX activity. All the synthesized compounds were docked inside the active site of the COX‐2 and LOX enzymes. They linked to COX‐2 through the N atom of the azole scaffold, while C?O of the oxazolone moiety was responsible for the binding to amino acids inside the LOX active site.

     

Discovery of a novel class of pyridine derivatives that selectively inhibits mutant isocitrate dehydrogenase 2

This paper presents synthesis and structure–activity relationship of pyridine derivatives as inhibitors of mutant isocitrate dehydrogenase 2 (IDH2). A series of 2,4,6‐trisubstituted pyridine derivatives have been prepared and evaluated in vitro. Among these compounds, 14n exhibited excellent inhibition activity with the IC₅₀ of 54.6 nm , which is approximately onefold improvement compared to drug candidate AG‐221 (Enasidenib) that is in Phase III trial. Exquisite selectivity of 14n for IDH2 R140Q mutant isoform was demonstrated by the poor activity against the wild‐type IDH1 and IDH2.     

新型川芎嗪衍生物的合成及其抗癌活性研究

目的合成新型川芎嗪衍生物并对其抗癌活性和毒性进行评价。方法以中医经典方药中抗癌活性成分为原料,利用拼合原理,设计、合成川芎嗪衍生物,并采用四甲基偶氮唑蓝(MTT)法体外检测川芎嗪衍生物对Hela(人宫颈癌)细胞模型的抗癌活性和对正常细胞MDCK(犬肾上皮细胞)的毒性。结果获得4个未见报道的川芎嗪类新化合物,均经光谱方法鉴定了结构,其中化合物10和12能明显抑制Hela细胞的增殖,抗癌活性显著高于其合成前体;且对MDCK细胞的毒性明显小于顺铂。结论该结果进一步验证以拼合原理为指导,从经典方药中发现新型低毒抗癌先导化合物的研究思路是可行的。     

EGCG及其衍生物的抗肿瘤作用研究进展

表没食子儿茶素没食子酸酯（EGcG）,是绿茶中的一种多酚类化合物,具有抗癌的功效。由于EGCG的安全性、廉价性、高效性等众多优点,使其受到广泛关注。本文综述了EGcG及其衍生物的抗肿瘤活性和作用机制。     

拉曼光谱快速检测加替沙星注射液

摘 要 目的： 建立用拉曼光谱技术快速鉴别和测定加替沙星注射液的方法。方法: 以加替沙星注射液为研究对象,运用拉曼光谱技术对加替沙星注射液进行快速鉴别和含量测定,测定条件：显微拉曼光谱仪,激发光波长:785 nm,物镜:50X,激光功率:3 mW,信号采集时间:60 s。结果:研究表明,拉曼光谱法可以鉴别加替沙星注射液,并能测定此类注射液中加替沙星含量分别为99.49%、97.56%、100.2%（规格：10 ml∶0.2 g）和97.75%、94.58%、96.25%（规格：2ml∶0.1 g）, 测定结果与HPLC法测定的结果差异无统计学意义（P>0.05）。结论: 本方法操作简便、快速无损,可作为加替沙星注射液快速检测的分析方法。     

姜黄素衍生物的合成方法研究进展

姜黄素是姜科和天南星科植物中广泛存在的一种色素,具有抗肿瘤、抗炎、抗氧化等活性,毒性低,但其临床应用因稳定性差、生物利用度低而受到限制。近年来,对姜黄素衍生物的合成方法主要分为两类,一是改变姜黄素的哥二酮结构或苯环结构,设计合成其类似物;二是在姜黄素结构中引入其他活性小分子。通过以上结构改造,能够有效改善姜黄素的稳定性、溶解度及生物活性,为其临床应用创造了良好的前景。