苦石莲化学成分研究

目的：系统研究苦石莲的化学成分，为进-步开发苦石莲和制定苦石莲药材定量分析标准提供科学根据。方法：利用硅胶、凝胶和制备薄层等常规色谱分离方法进行化合物分离，采用波谱技术和化学方法鉴定化合物的结构，并对苦石莲各萃取物、水溶部位和caesalmin C（化合物2）进行了流感甲型病毒活性的抑制作用试验。结果：从苦石莲乙醇提取物中分离得到9个化合物，分别鉴定为norcaesalnin E（化合物1）、caesalmin C（化合物2）、5-羟甲基-2-呋喃醛（化合物3）、胡萝卜苷（化合物4）、蔗糖（化合物5）、β-谷甾醇（化合物6）、硬脂酸（化合物7）、咖啡酸十八醇酯（化合物8）、2，5-二羟基苯甲酸乙酯（化合物9），活性试验结果表明，乙酸乙酯萃取物和化合物2对流感甲型病毒活性的抑制作用最强。结论：除化合物2外，其他8个化合物均为首次从该植物中分离得到；化合物2可以作为有效成分定量分析苦石莲质量。     

元宝草的化学成分研究

目的：对元宝草的化学成分进行研究。方法：利用硅胶、聚酰胺、Sephadex LH-20和大孔树脂柱层析对化合物进行分离，并利用光谱技术和理化性质进行结构鉴定。结果：从元宝草乙醇提取液的二氯甲烷萃取物中分离得到5个化合物，鉴定为二十八烷醇（octacosanol，化合物1）、三十烷酸（triacontanoic acid，化合物2）、豆甾醇（stigmasterol，化合物3）、苯甲酸（benzoic acid，化合物4）和1-羟基-7-甲氧基咕吨酮（1-hydroxy-7-methoxy-xanthone，化合物5）；从乙酸乙酯萃取物中分离得到3个化合物，鉴定为没食子酸（3，4，5-trihydroxy-benzoic acid，化合物6）、槲皮素（quercetin，化合物7）和1，3，6，7-四羟基咕吨酮（1，3，6，7-tetrahydroxy-xanthone，化合物8）。结论：除化合物7以外，其余7个化合物均为首次从元宝草中分离得到。     

中国南海海绵Plakortis sp.次生代谢产物研究

摘要：目的 研究海绵Plakortis sp.的次生代谢产物及其生物活性。方法 利用硅胶、HPLC等色谱学方法对海洋动物Plakortis sp.海绵进行分离纯化。通过NMR、MS、旋光等光谱学方法，并结合文献数据，确定化合物的结构。并对分离得到的化合物进行细胞毒，抗菌和抗HBV活性测试。 结果 共分离得到4个聚酮类化合物，结构确定为化合物1 6-desmethyl-6-ethyl-spongosoritin A、化合物2 6-desmethyl-6-ethyl-9,10-dihydrospongosoritin A、化合物3 methyl(2Z, 6R, 8S)-4,6-diethyl-3,6-3poxy-8-methyldodeca-2,4-dienoate、化合物4 spongosoritin A。 结论 化合物1～4为该海绵特征聚酮类代谢产物，细胞毒，抗菌和抗HBV活性结果显示，化合物1～4对金黄色葡萄球菌和大肠杆菌无生长抑制作用，对HCT-8、MCF-7、SMMC-7和HepG-2这四种癌细胞基本无生长抑制作用，化合物1～3基本无抗HBV活性，但化合物4表现出强烈的抗HBV活性。     

新型噁唑烷酮类化合物5-位侧链的结构改造及抗菌活性

目的对噁唑烷酮类化合物5-位侧链进行结构修饰与改造，并初步评价其体外抗菌活性。方法以间氟苯胺为原料，经9～12步反应合成目标化合物；采用二倍稀释法，测定目标化合物的体外抗菌活性。结果设计、合成了30个新化合物，其中目标化合物18个，其结构经^{1H NMR及MS等方法确证，11个化合物显示出不同程度的抗菌活性，化合物7a，9a和11a的活性较好。结论化合物7a，9a和11a值得进一步研究。}     

全氟烷酸类化合物的毒理学研究

全氟烷酸类化合物是一类新型的持久性有机污染物，已被广泛应用于工业生产以及生活用品中，在全球各地的环境介质和人群中均检测到了该化合物的存在，该类化合物的环境健康效应已经引起了广泛的关注。本文对该化合物的特征、来源、毒代动力学特征、毒性效应以及相关的机制进行了总结，以进一步了解该化合物毒理学方面的研究进展。     

地胆草倍半萜内酯化合物的结构修饰

为寻找毒性低、活性强的化合物，对地胆草倍半萜内酯化合物进行结构修饰。本文首先从地胆草全草中分离得到去氧地胆草内酯(deoxyelephantopin)和地胆草种内酯(scabertopin)，再对这两个化合物进行氧化和氢化反应，制备不同结构修饰产物。共得到5个大环化合物，通过IR、 ¹H NMR和MS等方法确定其结构。其中4个化合物(2～5)为新化合物，部分化合物有一定的抗肿瘤活性。     

PXR受体调控的CYP3A诱导及其在药物代谢中的重要意义

机体每日都要接触大量外源性化合物（xenobiotics），包括环境、饮食、药物中的各种成分，其中亲脂性化合物如果不能被及时代谢为极性化合物，就会在肝脏蓄积并影响机体正常生理功能，产生毒性甚至致癌。细胞色素P450（CYPS）属于血红素蛋白基因超家族，编码一系列代谢酶系统，参与各类不同结构亲脂性化合物的生物转化，增强代谢物水溶性，利于排出体外，     

海洋真菌095407的抗菌活性代谢产物的研究

目的对海洋真菌095407的抗菌活性成分进行研究。方法用多种色谱技术对化合物进行分离纯化，用光谱技术和理化性质鉴定化合物的结构，并用滤纸片琼脂扩散法测定化合物的抗耐甲氧西林金黄色葡萄球菌和白色念珠菌活性。结果从095407号真菌发酵液提取物中分离得到4个化合物，分别鉴定为3，4，5-三甲基-1，2-苯二酚（1）、decarboxydihydrocitrinone（2）、甘露醇（3）、刺芒柄花素（4）。结论化合物1为首次以天然产物的形式分离得到，活性测试结果表明化合物1和2具有抗耐甲氧西林金黄色葡萄球菌活性。     

万年蒿化学成分的研究

继前报作者又从蒿属植物万年蒿中（氯仿萃取部分，醋酸乙酯萃取部分和经大孔树脂乙醇洗脱部分）分得七个化合物。经理化学数测定，光谱分析鉴定化合物Ⅰ为东莨菪内酯，化合物Ⅱ为异秦皮定，化合物Ⅲ为琥珀酸，化合物Ⅳ为ｓｕｇｅｒｇｏｓｉｄ，化合物Ⅴ为万年蒿甙Ｃ，化合物Ⅵ为邻羟基桂皮酸酯甙和化合物Ⅶ为６－甲氧基－香豆素－７－羟基樱草甙，后者为首次从该属植物中分得的已知化合物。     

加拿大产西洋参的化学成分研究

目的 研究加拿大产西洋参（Panax quinquefolium）的化学成分。方法 采用硅胶和反相高效液相色谱法进行分离，通过理化性质和光谱数据，结合化学反应确定化合物结构。结果 从西洋参中分离得到8个化合物，其中化合物1为新化合物，结构确定为3β，6α，12β，20E-24，25-epoxy-3，12，23-trihydroxydammar-20（22）-en-6-O-α-L-rhamnopyranosyl（1→2）-β-D-glucopyranoside。其他化合物分别鉴定为人参皂苷-Rg6（2）、F1（3）、Rh1（4）、20（R）-Rh1（5）、Rg2（6）、Re（7）、Rb1（8）。结论 化合物1为首次分离得到的新化合物。化合物2和3为首次从该种植物中分离得到。     

1例肉碱棕榈酰转移酶2缺乏症报道并文献复习

目的：总结肉碱棕榈酰转移酶2（CPT2）缺乏症的诊治经验。方法：回顾性分析1例CPT2缺乏症患儿的临床资料和基因检测结果,并复习相关文献。结果：患儿,1岁7个月,第二次发病,两次临床表现主要为横纹肌溶解综合征,基因检测CPT2基因提示突变c.338C>T（p.S113L）和c.1711c>A（p.P571T）,c.338C>T（p.S113L）来自母亲,c.1711c>A（p.P571T）来自父亲,最终确诊为CPT2缺乏症。结论：反复发作的较小年龄横纹肌溶解综合征患儿需警惕遗传代谢病如CPT2缺乏症,通过基因检测做到早发现、早预防。     

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. I. Taxonomy of the producing organisms, fermentation and antimicrobial activity.

The dunaimycins are a new complex of spiroketal 24-membered macrolides discovered in the fermentation broth of two actinomycetes. Based on taxonomic studies these two cultures, which were isolated from soil, were identified as Streptomyces diastatochromogenes strains AB 1691Q-321 and AB 1711J-452. The dunaimycins possess both immunosuppressive and antimicrobial activity.     

Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents

A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.     

Stereospecificity of the inhibition by etomoxir of fatty acid and cholesterol synthesis in isolated rat hepatocytes

The racemates of substituted 2-oxiranecarboxylates are potent inhibitors of fatty acid oxidation and fatty acid and cholesterol synthesis. We show in the accompanying paper [Agius L, Peak M and Sherratt HSA, Biochem Pharmacol 42: 1711-1715, 1991] that only the R-enantiomer of etomoxir, a potent hypoglycaemic compound, inhibits fatty acid oxidation in hepatocytes. We demonstrate in this paper that although the R-enantiomer of etomoxir is esterified to its CoA-ester more readily than the S-enantiomer, both the R- and S-enantiomers are equally potent inhibitors of fatty acid and cholesterol synthesis from acetate in rat hepatocytes. The inhibition of fatty acid synthesis is not due to direct inhibition of fatty acid synthetase and the inhibition of cholesterol synthesis occurs at a site proximal to formation of mevalonate. Since the S-enantiomer inhibits fatty acid and cholesterol synthesis but not fatty acid oxidation the inhibition of the biosynthetic pathways is not coupled to inhibition of fatty acid oxidation.     

Why do physicians switch from one antipsychotic agent to another? The "physician drug stereotype"

There is a lack of research on why physicians select a certain drug in an individual case and not another available alternative, although this drug selection process is important for quality assurance and cost control. Four hundred ninety-five psychiatrists documented in a standardized form patient and illness characteristics of 1711 schizophrenic outpatients who were switched for individual clinical reasons from an ongoing neuroleptic treatment to olanzapine, and of another 1654 schizophrenic outpatients whose present neuroleptic medication was continued. Physicians also filled in the "Reason for Treatment Selection Questionnaire." Patients who were switched to olanzapine were more ill and showed more preexisting extrapyramidal symptoms and less patient compliance. Reasons of psychiatrists to switch to olanzapine were the expectation of better efficacy and tolerability of the present treatment and patient preferences to continue with the present medication. The price of olanzapine is seen as a reason not to select olanzapine but has no effect on the treatment decision. The "physician drug stereotype" of olanzapine corresponds with clinical data on the efficacy and tolerability of olanzapine. The data show that medical decisions about drug selection are multidimensional, integrating knowledge about the clinical properties of the drug, personal experiences and information about the individual case. The Reason for Treatment Selection Questionnaire is an instrument that allows to objectively assess important aspects of medical decision making, to generate psychological drug profile, and to understand why physicians prefer one drug over alternatives.     

Inhibition of phenol sulfotransferase (SULT1A1) by quercetin in human adult and foetal livers

1. Quercetin is one of the most abundant flavonoids in edible vegetables, fruit and wine. The aim was to study the type of inhibition of SULT1A1 by quercetin in the human adult and foetal livers. 2. The activity of SULT1A1 was measured with 4 microM 4-nitrophenol and 0.4 microM 3'-phosphoadenosine-5'-phosphosulphate-[(35)S], and its mean (+/-SD) and median were 769 +/- 311 and 740 pmol min(-1) mg(-1), respectively (adult liver, n = 10), and 185 +/- 98 and 201 pmol min(-1) mg(-1), respectively (foetal liver, n = 8, p < 0.0001). 3. In non-inhibited samples, K(m) for SULT1A1 (mean +/- SD) was 0.31 +/- 0.14 microM (adult liver) and 0.49 +/- 0.17 microM (foetal liver, n.s.). V(max) for SULT1A1 (mean +/- SD) was 885 +/- 135 pmol min(-1) mg(-1) (adult liver) and 267 +/- 93 pmol min(-1) mg(-1) (foetal liver, p = 0.007). 4. The IC(50) of quercetin for SULT1A1 was measured in three samples of adult and foetal livers and was 13 +/- 2.1 and 12 +/- 1.4 nM, respectively. 5. The type of inhibition was mixed non-competitive in adult and foetal livers and K(i) was 4.7 +/- 2.5 nM (adult liver) and 4.8 +/- 1.6 nM (foetal liver). 6. In the adult liver, the intrinsic clearance (mean +/- SD) was 3.3 +/- 1.5 ml min(-1) mg(-1) (non-inhibited samples), 0.9 +/- 0.4 ml min(-1) mg(-1) (12.5 nM quercetin) and 0.5 +/- 0.06 ml min(-1) mg(-1) (25 nM quercetin). In the foetal liver, the intrinsic clearance (mean +/- SD) was 0.5 +/- 0.2 ml min(-1) mg(-1) (non-inhibited samples), 0.12 +/- 0.01 ml min(-1) mg(-1) (12.5 nM quercetin) and 0.2 +/- 0.09 ml min(-1) mg(-1) (25 nM quercetin). 7. In conclusion, quercetin is a potent inhibitor of human adult and foetal liver SULT1A1. It reduces the sulphation rate and intrinsic clearance of 4-nitrophenol in both human adult and foetal livers. This suggests that quercetin may inhibit the sulfation rate of those drugs sulphated by SULT1A1. The inhibition of SULT1A1 is complex and not due solely to competition at the catalytic site of SULT1A1.     

Developmental toxic effects of N-ethyl-2-pyrrolidone administered orally to rats

The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses.     

在大鼠肝微粒体中反式曲马朵代谢及反式氧去甲基曲马朵生成的立体选择性(英文)

目的:研究反式曲马朵[(±)一trans-T]代谢及反式氧去甲基曲马朵(M1)生成的立体选择性,方法:(±)-trans-T及其对映体分别与大鼠肝微粒体孵育,高效毛细管电泳法测定孵育液中(±)-trans-T及M1对映体的浓度。结果:以(±)-trans-T单一对映体为底物孵育时,(+)-trans-T的代谢速率较低,(+)-M1生成有较低的V_(max)和CL_(int).以(±)-trans-T消旋体为底物孵育时,(±)-trans-T对映体的代谢速率及(±)-M1对映体的生成速率不同程度地减慢。右美沙芬、普罗帕酮和氟西汀既能抑制(±)-trans-T的代谢,又能抑制M1的生成;普罗帕酮和氟西汀能增强(±)-trans-T代谢及M1生成的立体选择性,右美沙芬仅使M1生成的立体选择性增强。结论:在大鼠肝微粒体中,(±)-trans-T代谢及M1生成有立体选择;(±)-trans-T对映体间存在相互作用。右美沙芬、普罗帕酮及氟西汀对它们的立体选择性产生不同的影响。