脱镁叶绿环类衍生物的分离,制备及鉴定

自蚕砂糊状叶绿素分得的叶绿素 a(1),于不同条件下经酸降解、脱羧焦化、甲酯化、氧化,在各步中可得脱镁叶绿素 a(2)、脱镁叶绿酸 a(3),焦脱镁叶绿酸 a(4)、甲基脱镁叶绿酸 a(5)、甲基焦脱镁叶绿酸a(6)、10-羟基甲基脱镁叶绿酸 a(7)和红紫素7-内酯二甲酯(8)。7和8的 ~1HNMR 和 MS 数据为首次报道。     

叶绿酸对某些毒物所致微核率的影响

叶绿酸是存在于天然食物和植物中叶绿素的钠、铜盐,是一种抗氧化剂。本研究用体外细胞系的双核微核试验法,研究叶绿酸对香烟烟雾凝聚物、苯并(a)芘、丝裂霉素C及硫酸镍微核率的影响。用上述毒物在加叶绿酸与不加叶绿酸条件下处理BALB/373细胞或CHL细胞,然后计数1000个双核细胞中的微核数。实验结果表明:叶绿酸具有抗香烟烟雾凝聚物微核形成的作用,并存在明显的剂     

脱镁叶绿酸的制备及其光敏抗菌活性

以初步纯化的叶绿素为原料,利用叶绿素酶水解、选择性酸降解两种方法制备脱镁叶绿酸。高效液相色谱分析显示两种方法得到的产物图谱相似,酸降解产物中脱镁叶绿酸A的含量较高。抗菌实验表明脱镁叶绿酸对革兰阳性菌具有光敏抑菌效果,对革兰阴性菌和酵母无明显作用。     

蚕沙粗品叶绿素酸降解产物的分离与鉴定

从蚕沙粗品叶绿素酸降解产物中分离制得在肿瘤中有选择性潴留作用,光动力学活性强于癌光啉的脱镁叶绿甲酯一酸 a 类组分混合物。经 HPLC 制备分离,~1H-NMR 和 MS 证明,它们为脱镁叶绿甲酯一酸 a(58%),脱镁叶绿甲酯一酸 a′(11%)和焦脱镁叶绿酸 a(31%)三种成分。     

蚕沙提取叶绿酸铜钠盐

叶绿酸铜钠盐(Sodium CopperChlorophyllin)为叶绿酸铜钠a与叶绿酸铜钠b两种盐的混合物,蓝黑色有金属光泽的粉末,有类似氨化合物臭气,易溶于水,微溶于乙醇、氯仿,几乎不溶于乙醚和石油醚。1％水溶液显深绿色,碱性(pH9.5～10.7)。本品水溶液或软膏用作除臭剂,可促进正常组织的恢复,解除创面发痒、溃疡、烧伤、皮炎,作用温和,无刺激性。50年代末开始用于治疗肝炎,目前市售的“肝宝”,每粒胶囊含叶绿酸铜钠20mg,据认为对肝脏网状内皮细胞有赋活作用,使肝功能     

叶绿酸铜钠抗突变作用的实验研究

用小鼠骨髓细胞微核试验和小鼠睾丸染色体畸变试验探讨叶绿酸铜钠的抗突变作用。结果：叶绿酸铜钠能有效地抑制由环磷酰胺诱导的小鼠ＰＣＥ微核的发生;在睾丸染色体畸变试验中,表现为对环磷酰胺诱导的小鼠精母细胞染色体畸变的抑制作用,由此表明,叶绿酸铜钠是一种有效的抗突变物质。     

铬叶绿酸钠的合成及临床试用初探

采用脱镁叶绿酸与铬络合后制成铬叶绿酸钠口服降糖药,并对１１例糖尿病患者在使用降糖药同时加用铬叶绿酸钠口服进行初步临床验证,观察患者血糖、血胆固醇（ＴＣ）、血甘油三酯（ＴＧ）水平的变化。结果证明铬叶绿酸钠降低血糖、血脂有一定作用。     

带有羧基侧链的苯(月弟)酸的合成

对羧甲基、对羧乙基、对羧甲氧基及4-羧基-3-羟基苯胺与亚硝酸重氮化,再与三氯化锑生成复盐,然后脱氮分解,形成相应苯(月弟)酸.这些(月弟)酸与呲啶及浓盐酸作用,便成吡啶复盐.复盐如溶于稀盐酸中,再加入浓盐酸盐析,水解便成精制(月弟)酸.吡啶复盐倘在盐酸及乙醇混合剂中重结晶,再在中性液中水解,便生成对乙氧羰甲基、对乙氧羰乙基、对乙氧羰甲氧基苯(月弟)酸.对甲氧羰基苯(月弟)酸与水合肼作用,酯键肼解而生成对肼羰基苯(月弟)酸.     

脱镁叶绿一酸a荧光特性研究

目的:研究中药蚕砂中脱镁叶绿一酸a的荧光性质。方法:采用丙酮提取,Al2O3柱层析和乙醚萃取自蚕砂中分离脱镁叶绿一酸a,采用荧光扫描确定其激发波长和发射波长,考察pH值、温度及光照时间对其荧光强度的影响。结果:脱镁叶绿一酸a的激发波长和发射波长分别为665和675 nm。pH碱性、提高温度可降低其荧光强度,光照则可提高其荧光强度。结论:脱镁叶绿一酸a在中性、酸性和低温条件下稳定,光照可加强其荧光效应。     

3-(氯甲基)-2-(3-苯乙酰胺-4-硫代苯磺酰-2-β-丙内酰胺-1-基) -3-丁烯酸对甲氧基苄酯的合成与表征

GCLE是合成头孢类抗生素的-种重要的中间体，3-（氯甲基）-2-（3-苯乙酰胺-4-硫代苯磺酰-2-p丙内酰胺-1-基）-3-丁烯酸对甲氧基苄酯经过-步反应即可得到GCLE。本文以自制3-甲基-2-（3-苯乙酰胺-4-硫代苯磺酰-2-β-丙内酰胺-1-基）-3-丁烯酸对甲氧基苄酯为原料，采用电解法得到目标产品。通过元素分析、IR对其结构进行表征，并用HPLC测定其含量。结果显示，此法合成GCLE工艺简单，收率高。     

Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages

Phenylpropanoids may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds. 4-cis, 8-cis-Bis (4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo-[3.3.0]octane-2,6-dione (bis-FA, compound 2), a dimer of ferulic acid, was synthesized from ferulic acid (1), and its effect on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells was compared with those of the parent ferulic acid (1) and of iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid) (3). LPS-induced gene expression of COX-2 was markedly inhibited by compound 2 at a concentration of 10 microM and by compound 3 at 100 microM, but was not inhibited by compound 1 at 100 microM. This observation suggests that compound 2 may possess potent anti-inflammatory activity. These ferulic acid-related compounds were able to scavenge the stable 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. The 50% inhibitory concentration for DPPH radicals declined in the order 3 (40.20 mM) > 2 (3.16 mM) > 1 (0.145 mM). Compound 1 possessed potent anti-radical activity, but no COX-2 inhibitory activity, which may be a result of enhancement of its conjugate properties by abstraction of an H atom from the phenolic OH group, causing loss of phenolic function. In contrast, inhibition of COX-2 expression by compounds 2 and 3 could be caused by their increased phenolic function, which is associated with decreased anti-radical activity. Compounds 2 and 3, particularly 2, may have potential as NSAID-like compounds.     

Lack of correlation between cigarette mainstream smoke particulate phase radicals and hydroquinone yield.

Evidence suggests that when compared with non-smokers, cigarette smokers are exposed to an increased burden of free radicals from both the vapor phase and particulate phase of the cigarette smoke aerosol. In this study, primary emphasis was placed on the free radicals found in the particulate phase. Published reports hypothesize that the particulate phase free radicals of cigarette mainstream smoke (MS) condensate consist of a hydroquinone/semiquinone/quinone shuttle. However, our results do not suggest that there is a positive correlation between the smoke yield of hydroquinone and the presence of particulate phase free radicals. First, 10-fold reductions in MS hydroquinone yield were obtained when KNO3 was applied to the surface of tobacco of an American blended cigarette. Surprisingly, there was no significant corresponding change in the yield of particulate phase radicals. Second, in experiments testing MS from low and high hydroquinone-yielding tobaccos there was no consistent corresponding relationship between hydroquinone and particulate phase radical yields. In one series of blends there was at best an inverse relationship between hydroquinone and particulate phase radical yields. In contrast with the published literature, we conclude that the particular compound or compounds driving particulate phase free radical formation are currently unknown. An additional experiment reported here suggested that components of the water soluble extract of burley tobacco may be driving the formation of particulate phase free radicals.     

酞丁安二氧六环包含物的研究

近年来,对包含化合物(inclusion compound亦称笼形物clathrate)的研究,进展甚快。由于其性质特殊,用途广泛,颇引起注意。本文通过对我国创制的治疗沙眼的新型药物(由中国医学科学院药物研究所研制的酞丁安,化学名为3-酞酰亚胺-2-氧代丁醛-双缩氨硫脲,并含有一定量的二氧六环,结构式为     

Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines

A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.     

Mechanism of inhibition of peroxynitrite-induced oxidation and nitration by [6]-gingerol

[6]-Gingerol potently inhibits peroxynitrite-induced oxidation and nitration reactions, but its mechanism of action is unclear. In order to discover the mechanism of inhibition, [6]-gingerol was reacted with peroxynitrite and the reaction mixture was analyzed using HPLC. The HPLC chromatogram showed one novel peak, indicative of the formation of a reaction product between [6]-gingerol and peroxynitrite. This compound was purified and identified as a symmetrical dimer of [6]-gingerol covalently linked at the aromatic ring. It has been assumed that this dimer is generated from a phenoxyl radical intermediate produced from [6]-gingerol via one-electron oxidation by peroxynitrite-derived radicals. We propose a mechanism in which [6]-gingerol scavenges peroxynitrite-derived radicals and consequently inhibits peroxynitrite-induced oxidation and nitration reactions.     

In vitro enzymatic evaluation of some pyrazolo[1,5-a]pyrimidine derivatives: Design,synthesis, antioxidant,anti-diabetic,anti-Alzheimer,and anti-arthritic activities with molecular modeling simulation

The strategy of utilizing nitrogen compounds in various biological applications has recently emerged as a powerful approach to exploring novel classes of therapeutics to face the challenge of diseases. A series of pyrazolo[1,5-a]pyrimidine-based compounds 3a–l and 5a–f were prepared by the direct cyclo-condensation reaction of 5-amino-1H-pyrazoles 1a, b with 2-(arylidene)malononitriles and 3-(dimethylamino)-1-aryl-prop-2-en-1-ones, respectively. The structures of the new pyrazolo[1,5-a]pyrimidine compounds were confirmed via spectroscopic techniques. The in vitro biological activities of all pyrazolo[1,5-a]pyrimidines 3a–l and 5a–f were evaluated by assaying total antioxidant capacity, iron-reducing power, the scavenging activity against 1-diphenyl-2-picryl-hydrazyl (DPPH) and 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, anti-diabetic, anti-Alzheimer, and anti-arthritic biological activities. All compounds displayed good to potent bioactivity, and three compounds 3g, 3h , and 3l displayed the most active derivatives. Among these derivatives, compound 3l exhibited the highest antioxidant (total antioxidant capacity [TAC] = 83.09 mg gallic acid/g; iron-reducing power [IRP] = 47.93 µg/ml) and free radicals scavenging activities with (DPPH = 18.77 µg/ml; ABTS = 40.44%) compared with ascorbic acid (DPPH = 4.28 µg/ml; ABTS = 38.84%). Furthermore, compound 3l demonstrated the strongest inhibition of α-amylase with a percent inhibition of 72.91 ± 0.14 compared to acarbose = 67.92 ± 0.09%. Similarly, it displayed acetylcholinesterase inhibition of 62.80 ± 0.06%. However, compound 3i showed a significantly higher inhibition percentage for protein denaturation and proteinase at 20.66 ± 0.00 and 26.42 ± 0.06%, respectively. Additionally, some in silico ADMET properties were predicted and studied. Finally, molecular docking simulation was performed inside the active site of α-amylase and acetylcholinesterase to study their interactions.     

Synthesis and biological studies of some benzopyran

3-Chlorobenzopyrano[2,3-c]pyrazole (2) was prepared and reacted with sodium azide to give compound 3, whereas its reaction with benzoyl hydrazide, ethyl glycinate, anthranilic acid or o-phenylenediamine afforded the products 4-7, respectively. Compounds 8 and 9 were synthesized by the reaction of compound 2 with 2-mercaptobenzothiazole or piperidine. 3-Hydrazinobenzopyrano[2,3-c]pyrazole (10) was obtained and subjected to cyclization with different reagents such as CS2, benzoic acid, acetyl acetone and diethyl malonate to give compounds 11-14, respectively. Compound 10 was cyclized also with phenacyl cyanide, ylidenemalononitriles to afford the products 15-20, respectively. On the other hand, compound 10 was cyclized with 3-[bis(methylthio)methylene]pentane-2,4-dione or 1,1-dicyano 2,2-dimethylthioethylene to give the corresponding compounds 22 and 23 which in turn were reacted with some compounds containing active methylene groups to afford the corresponding compounds 24-27, respectively. The biological activities of someselected compounds were given.     

Extra-vesicular binding of noradrenaline and guanethidine in the adrenergic neurones of the rat heart: a proposed site of action of adrenergic neurone blocking agents.

1 The binding and efflux characteristics of [14C]-guanethidine and [3H]-noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. 2 Binding of both compounds occurred at extra-vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]-guanethidine and [3H]-noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. 3 (+)-Amphetamine accelerated the efflux of [14C]-noradrenaline; this effect was inhibited by desipramine. 4 Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]-guanethidine but not that of [3H]-noradrenaline. 5 Heart slices labelled with [3H]-noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in in these slices. 6 It is suggested that [14C]-guanethidine and [3H]-noradrenaline are bound at a common extravesicular site within the adrenergic neurone. Binding of guanethidine to the extra-vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.     

Activity of acyclic halogenated tubercidin analogs against human cytomegalovirus and in uninfected cells.

Novel acyclic halogenated tubercidins (4-amino-5-halo-7-[(2-hydroxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidines) were examined for their ability to inhibit human cytomegalovirus (HCMV) in yield reduction assays. 5-Bromo acyclic tubercidin (compound 102) was a more potent inhibitor of virus replication than the chloro- and iodo-substituted analogs (compounds 100 and 104). At a 100 microM concentration, the bromo and chloro compounds were more potent than acyclovir but not ganciclovir. Virus titers were reduced more than 99% by compounds 102 and 104 whereas compound 100 and the equally potent acyclovir reduced titers by only 90%. Quantitation of viral DNA by DNA hybridization demonstrated strong inhibition of HCMV DNA synthesis by these compounds. The most potent inhibitor, compound 102, had a 50% inhibitory (I50) concentration (1.6 microM) comparable to that of ganciclovir (1.8 microM). Cytotoxicity in uninfected human cells was evaluated and revealed the following: cell growth rates slowed markedly in the presence of 10 microM compound 102 whereas the same concentration of compounds 100 and 104 led to only a slight prolongation of population doubling time; these compounds inhibited cellular DNA synthesis but not RNA or protein synthesis, as measured by incorporation of radiolabeled precursors into acid-precipitable macromolecules; flow cytometry indicated that compound 102 was a mid-S phase blocker, and adenosine antagonized the inhibition of [3H]dThd incorporation by compound 102. Together, these results demonstrate that compound 102 is a potent and selective inhibitor of viral and cellular DNA synthesis and that acyclic halogenated pyrrolo-pyrimidine nucleosides may have therapeutic potential.