2，3-二氢-1-氨基-2-羟基-4-硝基茚的合成研究

最近几年,国外开发了不少以茚为母体的系列药物和兽药。如：以系列抗HIV药物L-689,502;L-685,927;L-735,524等、系列平滑肌迟缓药SARs及系列抗精神分裂药物。此外,作为农药应用,有日本开发的除草剂一茚草酮及美国杜邦公司于1992年开发,并于2001年登记上市的氨基甲酸酯类杀虫剂——茚虫威等。     

傣药翅荚决明树皮中1个新呋喃-2-甲酸类化合物

对傣药翅荚决明Cassia alata树皮的化学成分进行研究。运用硅胶、凝胶、MCI-gel树脂及RP-HPLC等多种色谱技术从翅荚决明树皮95%乙醇提取物中分离鉴定了1个新呋喃-2-甲酸类化合物,鉴定为5-[3-(羟甲基)-4,5-二甲氧基苯]-3-甲基呋喃-2-甲酸(1)。生物活性测试中,其对NB4,A549,SHSY5Y,PC3和MCF7的IC50分别为2.5,1.2,2.2,3.6,1.9μmol·L~(-1)。化合物1为新化合物,并且表现出一定的细胞毒活性。     

铁皮石斛1-羟基-2-甲基-2-(E)-丁烯基-4-焦磷酸还原酶基因的克隆与表达分析

目的从铁皮石斛Dendrobium officinale中克隆1-羟基-2-甲基-2-(E)-丁烯基-4-焦磷酸还原酶[1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphatereductase,HDR]基因,并分析其在铁皮石斛不同组织中的表达差异以及不同信号分子诱导下的表达模式。方法采用RT-PCR和RACE等方法获得铁皮石斛HDR基因(Do HDR)全长,利用DNAMAN和MEGA6.0对其他物种的HDR基因编码的氨基酸序列进行同源性分析和进化关系分析,使用实时荧光定量分析HDR基因的表达模式。结果成功获得Do HDR基因,Gen Bank登录号为KC344827,全长1 658 bp,编码460个氨基酸,与其他科属植物的同源性达到80%以上。Do HDR基因在铁皮石斛叶片中表达量最高,从高到低依次是根、茎、原球茎;且受到脱落酸(abscisic acid,ABA)、水杨酸(salicylic acid,SA)信号分子的诱导。结论从铁皮石斛中获得Do HDR基因,为进一步阐明铁皮石斛萜类化合物合成途径中该基因的重要作用奠定了理论基础。     

2-氨基磷酸茚处理对新疆紫草悬浮细胞次生代谢物积累的影响

用不同浓度2-氨基磷酸茚(AIP),并结合茉莉酸甲酯(Me JA)处理新疆紫草悬浮细胞,测定不同处理组、不同处理时间细胞中迷迭香酸及乙酰紫草素、脱氧紫草素、β,β'-二甲基丙烯酰紫草素、异戊酰紫草素等次生代谢物的含量,考察AIP抑制苯丙氨酸通路后对紫草悬浮细胞中次生代谢物合成、积累的影响。结果显示Me JA处理能够明显促进新疆紫草细胞中次生代谢物的合成积累;AIP处理能够抑制新疆紫草细胞中上述次生代谢物的积累,并在二者联合处理时能一定程度上抵消Me JA的促进作用,且抑制作用的强弱与处理剂量、处理时间存在正相关性。表明苯丙氨酸途径在紫草素类化合物生物合成中具有重要作用,可为通过细胞培养方式生产紫草素类化合物的代谢调控及紫草素类化合物生物合成等进一步研究提供参考。     

4-羟基苯并恶唑-2-酮对小鼠急性肝损伤的保护作用

目的研究4-羟基苯并恶唑-2-酮(4-hydroxy-2-benzoxazolone,简称HBOA)对四氯化碳所致小鼠急性肝损伤的保护作用,并探讨其疗效机制。方法采用腹腔注射四氯化碳(Carbon tetrachloride,CCl4)制备小鼠急性肝损伤模型,HBOA灌胃给药,检测小鼠血清中的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性以及肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)含量,观察光镜下肝组织的病理变化。结果 HBOA能明显降低CCl4致急性肝损伤小鼠血清ALT、AST活性,同时升高肝组织中SOD、GSH的活性,降低肝组织MDA的含量;减轻肝组织坏死程度。结论 HBOA对CCl4所致小鼠急性肝损伤有一定的保护作用,其保护机制可能与其抗脂质过氧化有关。     

4-羟基苯并恶唑-2-酮对HSC-T6细胞增殖的影响

目的研究4-羟基苯并恶唑-2-酮(HBOA)对HSC-T6细胞增殖的影响。方法 HSC-T6细胞分别在药物处理组(HBOA浓度分别为0.008,0.04,0.2,1,5 mg/ml)及对照组(单纯培养液)中体外培养32 h。应用四甲基偶氮唑盐法(MTT法)检测细胞增殖情况;荧光倒置显微镜下观察对照组和药物处理组HSC-T6细胞的形态学变化。结果药物处理组HSC-T6细胞的增殖率均低于对照组,浓度为0.008 mg/ml的药物处理组与对照组相比无显著性差别(P>0.05);其他药物处理组分别与对照组比较能显著地抑制细胞增值(P<0.05或P<0.01)。HBOA对HSC细胞的增殖抑制率均随着药物作用浓度的升高而逐渐升高;经吖啶橙染色后,在荧光倒置显微镜下观察,均可见细胞数量减少、体积缩小、核破裂、核浓缩等变化,且随着作用浓度的增加变化更加明显。结论 HBOA对HSC-T6细胞具有抑制增殖的功效。     

1-羟基-2,3,5-三甲氧基-酮对脂多糖致小鼠急性肺损伤的保护作用

目的探讨1-羟基-2，3，5-三甲氧基[口山]酮（QGS）对脂多糖（LPS）致小鼠急性肺损伤的保护作用及其机制。方法采用ipLPS的方法建立小鼠急性肺损伤模型。检测肺脏指数，酶法检测支气管及肺泡灌洗液（BALF）中NO水平，Westernblotting法检测核转录因子κB抑制蛋白IκB—α，诱导型一氧化氮合成酶（iNOS）及环氧合酶Ⅱ（COX-2）等蛋白的表达，HE染色观察肺组织病理学改变。结果QGS500mg／kg组能显著降低LPS引起的小鼠的肺脏指数（P〈0．05）。QGS250、500mg／kg组均能显著降低LPS致伤小鼠BALF中NO水平，抑制率分别达到了37％和48．1％。同时QGS500mg／kg组还能够明显增加肺组织中IκB—α蛋白表达量并下调iNOS及COX-2蛋白表达量。结论QGS对LPS引起的小鼠急性肺损伤有保护作用，该作用与其增加IκB—α蛋白表达而抑制iNOS和COX-2蛋白的表达有关。     

10-羟基-2-癸烯酸治疗实验性高脂血症大鼠的药理研究

目的:本实验研究蜂王酸即10-羟基-2-癸烯酸(10-Hydroxy-2-Decenoic Acid,10-HDA)对治疗实验性高脂血症大鼠的药理作用。方法:通过喂养高脂食物建立高脂血动物模型,测定10-HAD对高脂血动物预防给药及治疗给药的作用。结果:10-HAD具有明显降低实验性高脂血症大鼠血液中甘油三酯(TG)、总胆固醇(TC)、β-脂蛋白含量,同时升高高密度脂蛋白(HDL)含量,说明10-HDA对高脂血症具有良好的治疗作用。结论:10-HAD是蜂王浆治疗高脂血症中的功能因子。     

HPLC测定双参安神糖浆中10-羟基-2-癸烯酸的含量

双参安神糖浆是由人参、党参、当归、麦冬、枸杞、何首乌、蜂王浆等中药组成。蜂王浆中含有多种羟基酸,其中10-羟基2-癸烯酸(10-hydroxy-α-decenoic acid,10-HDA)含量较高,其含量已成为蜂王浆贸易中最重要的指标之一,测定10-HDA具有重要的实际意义,有关10-HDA测定已有报道[1~4],原双参安神糖浆质量标准中是采用薄层扫描法测定10-羟基-2-癸烯酸的含量,但薄层扫描法测定影响因素多,较难控制,导致含量测定结果不够准确。我们采用HPLC法进行了尝试,并对HPLC法测定双参安神糖浆中10-羟基-2-癸烯酸含量的方法学进行了考察。该法简便易行,…     

1-羟基-2,3,5-三甲氧基(口山)酮对脂多糖致小鼠急性肺损伤的保护作用

目的探讨1-羟基-2,3,5-三甲氧基■酮(QGS)对脂多糖(LPS)致小鼠急性肺损伤的保护作用及其机制。方法采用ipLPS的方法建立小鼠急性肺损伤模型。检测肺脏指数,酶法检测支气管及肺泡灌洗液(BALF)中NO水平,Western blotting法检测核转录因子κB抑制蛋白IκB-α,诱导型一氧化氮合成酶(iNOS)及环氧合酶Ⅱ(COX-2)等蛋白的表达,HE染色观察肺组织病理学改变。结果QGS500mg/kg组能显著降低LPS引起的小鼠的肺脏指数(P<0.05)。QGS250、500mg/kg组均能显著降低LPS致伤小鼠BALF中NO水平,抑制率分别达到了37%和48.1%。同时QGS500mg/kg组还能够明显增加肺组织中IκB-α蛋白表达量并下调iNOS及COX-2蛋白表达量。结论QGS对LPS引起的小鼠急性肺损伤有保护作用,该作用与其增加IκB-α蛋白表达而抑制iN-OS和COX-2蛋白的表达有关。     

高效液相色谱同时测定荷叶药材及其生物碱部位中4种生物碱的含量

目的：建立测定荷叶药材及其生物碱部位中4种生物碱类成分2-羟基-1-甲氧基阿朴啡、原荷叶碱、荷叶碱和莲碱含量的高效液相色谱方法。方法：采用Hypersil C₁₈柱(4.6 mm×250 mm，5 μm)，以乙腈-0.1%三乙胺水溶液为流动相，梯度洗脱，流速1.0 mL·min^-1，柱温35 ℃，检测波长270 nm。结果：2-羟基-1-甲氧基阿朴啡、原荷叶碱、荷叶碱和莲碱的线性范围分别为0.110～0.658 μg(r=0.999 5)，0.021～0.126 μg(r=0.999 5)，0.103～0.618 μg(r=0.999 8)，0.086～0.514 μg(r=0.999 5)，荷叶生物碱部位平均加样回收率(n=6)分别为101.5%，99.14%，99.21%，98.41%；荷叶药材平均加样回收率(n=6)分别为99.53%，100.5%，97.51%，100.1%。 结论：3批样品测定结果表明，该方法简便准确，可用于荷叶药材及其生物碱部位中4种生物碱类成分的含量测定。     

甘草次酸/11-脱氧甘草次酸甲酯的合成

以甘草次酸为原料,采用经典的克莱门森还原制备了11-脱氧甘草次酸,接着在不同的催化体系中(浓硫酸、浓盐酸、干盐酸气)研究了合成了甘草次酸甲酯的最佳条件,结果表明以干盐酸气催化可获得较高的产率。并在该条件下合成了11-脱氧甘草次酸甲酯。合成的化合物经过IR,1HNMR,13CNMR等进行了表征。     

齐墩果酸对健康人体CYP1A2,CYP2E1及CYP3A4抑制作用的研究

 目的在人体内研究齐墩果酸对CYP1A2,CYP2E1及CYP3A4酶活性的影响,以预测齐墩果酸与常用临床药物的相互作用。方法分别以咖啡因、氯唑沙宗和咪哒唑仑作为CYP1A2,CYP2E1及CYP3A4的探药,采用随机、开放、双周期交叉设计,12名健康男性受试者在服用7d齐墩果酸前后均服用100mg咖啡因、400mg氯唑沙宗和7.5mg咪哒唑仑,服探药后采血测定探药及相应代谢产物的浓度,并计算相关参数。探药和代谢物的浓度分别用RP-HPLC和HPLC-MS测定。结果服用齐墩果酸7d后,咖啡因的代谢受到显著的抑制,其达峰时间、消除半衰期及药-时曲线下面积显著增加;氯唑沙宗的代谢受到轻微抑制,达峰浓度、达峰时间、消除半衰期及药-时曲线下面积均有升高趋势,但无显著性差异;咪哒唑仑的代谢未受影响。结论服用7d齐墩果酸对CYP1A2体内活性有显著抑制作用,对CYP2E1体内活性有轻微抑制作用,而对CYP3A4酶活性无影响。     

龙骨马尾杉PcHDR1基因克隆及序列分析

该研究采用RT-PCR方法对龙骨马尾杉Phlegmarirus carinatus(Desv.)Ching 1-羟基-2-甲基-2-(E)-丁烯基-4-焦磷酸还原酶[1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase,HDR]基因Pc HDR1的编码区进行克隆并利用生物信息学方法进行序列分析。根据实验室已获得的龙骨马尾杉转录组数据,从中获得1条编码HDR的转录本,采用RT-PCR方法获得该基因的全长c DNA序列,所克隆的Pc HDR1基因编码区长为1 437 bp,编码478个氨基酸残基,Gen Bank登录号为JQ957845。Pc HDR1与银杏Ginkgo biloba的HDR序列同源性最高,达78%。生物信息学预测Pc HDR1蛋白没有跨膜区,具有Lyt B保守结构域,不含信号肽。该研究克隆并获得了龙骨马尾杉Pc HDR1基因的编码区序列,并对其编码的蛋白进行了序列分析及结构域预测,为进一步研究HDR的功能奠定基础。     

1-hydroxy-2,3,4,6-tetramethoxy-xanthone对大鼠局灶性脑缺血再灌注损伤的保护作用

目的 :研究 1 hydroxy 2 ,3 ,4,6 tetramethoxy xanthone对大鼠局灶性脑缺血再灌注损伤的保护作用。 方法 :采用线栓法阻断大脑中动脉 (MCA)血流 ,造成局灶性脑缺血再灌注模型 (MCAO) ;评价大鼠神经行为功能、测定脑梗塞体积及血清中丙二醛(MDA)含量、超氧化物歧化酶 (SOD)和谷胱甘肽过氧化物酶 (GSH Px)活性。结果 :与大鼠脑缺血再灌注模型组相比 ,1 hydroxy 2 ,3 ,4,6 tetramethoxy xanthone能明显降低脑缺血再灌注大鼠的神经行为学评分分值 (P <0 .0 5 ) ,缩小脑梗塞灶体积 (P <0 .0 1) ,显著提高SOD、GSH Px的活力 (P <0 .0 5 ) ,降低MDA含量 (P <0 .0 5 )。结论 :1 hydroxy 2 ,3 ,4,6 tetramethoxy xanthone对大鼠脑缺血再灌注损伤具有保护作用 ,其作用机制可能与提高SOD、GSH Px的活性 ,减少脂质过氧化有关。     

2-乙基-3-羟基-6-苯硫基-4(1H)-吡啶酮对四氯化碳损伤原代培养大鼠肝细胞的影响

目的 研究2－乙基－3－羟基－6－苯硫基－4（1H）－吡啶酮（HPP）对四氯化碳（CCl4）损伤原代培养大鼠肝细胞的保护作用。方法 原位灌流法分离大鼠肝细胞培养24h后加入HPP，同时造成CC4损伤，于损伤后24h和48h测培养液中丙二醛（MDA）含量、谷丙转酶氨酶（ALT）、谷胱甘肽过氧化物酶（GSH－Px）的活性，48h后用MTT法测肝细胞存活率。结果 HPP对GPT在力的升高有抑制作用，同时抑制MDA的产生及肝细胞损伤造成的GSH－Px活力的降低。结论 HPP能有效抑制CCl4造成的原代培养在鼠肝细胞损伤。     

Bioactivities and Pharmaceutical Effects of 1-Aminocyclopro- panecarboxylic Acid

作 者：

ZHU Qin-wei    KRAEMER Alexander    ZHU Xu-xiang  

作者单位：

Faculty of Public Health,Bielefeld University,Bielefeld 33615,Germany 

期 刊：

中草药（英文版）    

Journal：

CHINESE HERBAL MEDICINES  

年,卷(期)：

2010, 02(2) 

分类号：

R2 

Keywords：

1-aminocyclopropanecarboxylic acid    bioactivities    cerebro- and cardiovascular    neurological protection    non-protein acid    pharmaceutical effects   

机标分类号：

R96 R97 

机标关键词：

neuroprotective effectscardiovascular systemlearning and memorydetermination ofclinical trialsstudiesnervous systemsignificanceamino acidglutamatedifferentcountriesAbstractsresearcharticlesvarietyResultsnaturalMedlinemedical 

基金项目：

 

DOI：

10.3969/j.issn.1674-6384.2010.02.001 

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