吲哚脲类化合物的设计合成及其体外抗肿瘤活性研究

目的以索拉非尼为先导物,设计并合成一系列吲哚脲类化合物,并对其体外抗肿瘤活性进行初步评价。方法以5-硝基吲哚-2-甲酸为起始原料,采用BOP法合成酰胺,再将硝基还原成胺基,最后与异氰酸酯缩合,共3步反应制备目标化合物;采用MTT法评价目标化合物对4种肿瘤细胞株(MX-1、A375、HepG2、Ketr3)的生长抑制作用。结果与结论合成了28个吲哚脲类新化合物,其结构经1H-NMR和HR-MS确证。体外活性结果表明,与索拉非尼相比多数化合物选择性地作用于MX-1细胞株,显示出较强的抑制肿瘤细胞增殖的活性。其中含甲基哌啶的化合物26、30和31抑制MX-1和A375细胞生长的作用显著强于索拉非尼。尤其是化合物31抑制A375细胞增殖的作用是索拉非尼的10倍,对HepG2的抑制活性与索拉非尼相当,IC50值均达到微摩尔级水平,值得进一步研究。     

酶法-超声提取黄精总黄酮及其抗氧化活性研究

目的 研究酶法-超声提取黄精中总黄酮（total flavonoids from Polygonatum sibirici,TFPS）的最佳工艺及总黄酮的体外抗氧化活性。方法 以总黄酮含量为指标,采用单因素和正交试验对纤维素酶用量、乙醇浓度、液料比和超声时间进行考察,优化工艺条件并考察总黄酮对DPPH自由基、ABTS⁺自由基的清除能力和亚铁离子螯合活性。结果 最佳提取条件：纤维素酶用量为0.75%,乙醇浓度为40%,液料比为20 mL·g^-1,超声时间30 min,总黄酮含量为1.595%。体外抗氧化试验表明,黄精总黄酮对DPPH自由基、ABTS⁺自由基有很强的清除能力,IC₅₀分别为27.55,11.47 μg·mL^-1,对亚铁离子的螯合活性较强,IC₅₀为32.26 μg·mL^-1。结论 酶法-超声提取工艺具有提取效率高、稳定性及重复性好等优点,可用于黄精中总黄酮的提取,在该工艺下提取的总黄酮具有较强的抗氧化活性。     

小檗碱及其衍生物的研究进展

小檗碱是从中草药黄连等植物中提取分离得到的一类异喹啉类生物碱。近十年来，已经有2 000多篇国内外文献报道了小檗碱及其衍生物在治疗肿瘤、糖尿病、心血管疾病、高血脂、炎症、细菌和病毒感染、脑缺血性损伤、精神疾病、阿尔茨海默病(Alzheimer disease)、骨质疏松等多方面的临床应用、药效机制以及该类化合物的构效关系等研究结果。这些结果表明小檗碱生理功能广泛，潜在的结构改造和开发应用价值很大，但还未见系统的回顾和综述。本文对这些文献进行了系统地分析整理，主要从临床应用与药效机制、分子药理、体内吸收代谢、构效关系四个方面来介绍小檗碱及其衍生物的研究进展，旨在为进一步深入开展以药效机制为基础的小檗碱结构改造和创新药物研究提供比较系统的信息。     

京都酚的致惊作用

京都酚为-中枢神经系统活性二肽,icv可使小鼠出现惊厥。右旋京都酚致惊活性明显强于左旋体。利血平化动物明显增强京都酚的致惊作用,对于京都酚在利血平化小鼠所引起的惊厥,L-Dopa可使之减弱。5-HTP及纳洛酮可使之增强;抗癫痫药中硝基安定、苯妥英钠和丙戊酸钠可明显延长发作潜伏期,缩短持续时间和减少发作率。     

Binding and Anticancer Properties of Plumbagin with Human Serum Albumin

Plumbagin has received extensive attention as a promising anticancer drug. Therefore, we investigated the binding and anticancer properties of plumbagin with human serum albumin. Fluorescence results demonstrated that plumbagin interacts with human serum albumin, although its binding affinity may be affected to various extents by different compounds. The human serum albumin–plumbagin complex structure revealed that plumbagin binds to the hydrophobic cavity in the IIA subdomain of human serum albumin through hydrogen bonding and hydrophobic interactions. The plumbagin–human serum albumin complex enhances cytotoxicity by 2‐ to 3‐fold particularly in cancer cells but has no effect on normal cells in vitro. Compared with the unbound drug, the human serum albumin–plumbagin complex promotes HeLa cell apoptosis and has a stronger capacity for cell cycle arrest at the G2/M phase of HeLa cells. In conclusion, this study contributes to the rational design and development of plumbagin‐based drugs and a drug–human serum albumin delivery system.     

国产CEFTAZIDIME的微生物学评价

本文报道国产Ceftazidime对临床分离681株致病菌进行体内外抗菌活性研究,并与头孢噻肟、头孢三嗪、Moxalactam、头孢哌酮、Cefsulodin、头孢孟多、头孢唑啉、头孢噻吩、哌拉西林、替卡西林、庆大霉素及丁胺卡那霉素的抗菌作用进行比较。实验证明Ceftazidime与第三代头孢菌素的抗菌活性相似,其独特之处是抗绿脓杆菌活力强,对400株绿脓杆菌的MIC_(50)、MIC_(90)及MIC_(Gm)分别为1.6、3.2及1.57μg/ml。对121株多种耐药绿脓杆菌,有98.4％的菌株敏感。对小鼠感染绿脓杆菌有明显治疗效果,其ED_(50)为3.09～4.14mg/kg。结果表明:Ceftazidime抗绿脓杆菌作用极强,显著优于其他抗生素,为临床治疗绿脓杆菌感染的重症患者提供了一个新抗生素。     

Composition,antimicrobial activity and in vitro cytotoxicity of essential oil from Cinnamomum zeylanicum Blume (Lauraceae)

The essential oil from the bark of Cinnamomum zeylanicum Blume was analyzed by GC–MS and bioassays were carried out. Nine constituents representing 99.24% of the oil were identified by GC–MS. The major compounds in the oil were (E)-cinnamaldehyde (68.95%), benzaldehyde (9.94%) and (E)-cinnamyl acetate (7.44%). The antimicrobial activity of the oil was investigated in order to evaluate its efficacy against 21 bacteria and 4 Candida species, using disc diffusion and minimum inhibitory concentration methods. The essential oil showed strong antimicrobial activity against all microorganisms tested. The cytotoxic and apoptotic effects of the essential oil on ras active (5RP7) and normal (F2408) fibroblasts were examined by MTT assay and acridine orange/ethidium bromide staining, respectively. The cytotoxicity of the oil was quite strong with IC₅₀ values less than 20 μg/mL for both cell lines. 5RP7 cells were affected stronger than normal cells. Morphological observation of apoptotic cells indicated the induction of apoptosis at the high level of the oil, especially in 5RP7 cells. The present study showed the potential antimicrobial and anticarcinogenic properties of the essential oil of cinnamon bark, indicating the possibilities of its potential use in the formula of natural remedies for the topical treatment of infections and neoplasms.     

一株采自新疆虫草体内的真菌的分离鉴定及其抑菌作用研究

目的研究从新疆虫草(Ophiocordyceps gracilis(Grev.)G.H.Sung,J.M.Sung,Hywel-Jones&Spatafora)体内分离得到一株真菌SFYC003。方法经生理生化特征、形态学和ITS序列对比分离鉴定菌株,采用滤纸片法研究了该菌株的菌体及其发酵液对6株供试菌的抑制作用。结果所得菌株属于青霉属真菌变灰青霉(Penicillium canescens)的一个变种,命名为SFYC003,其对大肠埃希菌和金黄色葡萄球菌供试菌的抑菌活性较强。结论菌株SFYC003具有进一步研究及开发利用的潜在价值。     

天然药物成分致突变性风险预测与评价方法研究进展

天然药物成分复杂，无法逐一完成系统的致癌性风险评价及体内遗传毒性试验。鉴于计算机毒理学结合体外致突变风险评价方法在遗传毒性杂质致突变性评价方面的快速发展，也可考虑将此评价模式应用于天然药物成分的致突变性筛选与机制研究。从计算机毒理学和体外致突变性评价两方面出发，综述天然药物致突变性的研究方法，为其遗传毒性试验评价及监管提供借鉴。