抗寄生虫药物硝硫氰胺类似物的合成

本文报道52个硝硫氰胺的衍化物,经对小鼠抗日本血吸虫筛选结果表明,其中8个化合物有抗日本血吸虫作用。化合物23对家兔血吸虫病的疗效较硝硫氰胺明显为高。对其中的6个化合物经棉鼠丝虫病实验治疗,发现化合物2和26有抗丝虫病作用,化合物26对微丝蚴和成虫的杀灭作用,不亚于海群生。药理研究正在进行中。     

吡喹酮衍生物S83143及其盐类对小鼠血吸虫的杀灭作用

吡喹酮衍生物S83143及其无机盐类S85009,S85010和S85021对小鼠体内2h血吸虫童虫和血吸虫成虫均有明显的杀灭作用,但对3～14d童虫的作用不明显。S83143难溶于水,毒性甚低,其形成盐类后可溶于水,毒性则明显增加。S83143硫酸盐S85010抗血吸虫的有效剂量接近或大于1/2LD_(50),故该化合物的实用意义不大。     

抗血吸虫药1-(5-硝基-2-噻吩亚甲氨基)咪唑烷-2-酮及其类似物的合成

1-(5-硝基-2-噻吩亚甲氨基)-咪唑烷-2-酮(1)具有抗曼氏血吸虫作用。考虑其结构与硝唑咪相似,推测该化合物可能也具有抗日本血吸虫作用,故合成了该化合物及其类似物。药理筛选证明,1确有较显著的抗日本血吸虫作用。     

血吸虫病化学治疗的研究——ⅩⅩⅤ.取代香豆素-3-羧酸酯和酰胺衍生物的合成

香豆素含有内酯结构时,可能有驱蠕效力。因此合成了取代香豆素-3-羧酸酯与酰胺化合物57个,经动物筛选发现6个化合物在感染日本血吸虫的小白鼠体内有显著驱蠕虫作用,其中以6-溴-香豆素-3-羧酸乙酯杀虫效力最强,试用于临床,证明有一定疗效。     

合成药物

122.具有杀血吸虫作用的硝基噻吩类化合物作者介绍了一类具有杀血吸虫作用的硝基噻吩化合物,并对Bueding等建立的硝基杂环化合物与杀血吸虫之间构效关系方面的假说作出了补充。作者制备了硝基杂环与含氮取代基间的桥基为次甲基亚胺的硝基噻吩和硝基呋喃化合物,经杀虫作用比较,发现硝基噻吩类化合物具有杀死隐栖在小白鼠门静脉处的曼氏血     

血吸虫病化学治疗的研究——ⅩⅩⅩⅦ.β-(5-硝基-4-溴-2-呋喃)-及β-(4,5-二溴-2-呋喃)丙烯酰胺及其酯类的合成

本文报道β-(4,5-二溴-2-呋喃)-及β-(5-硝基-4-溴-2-呋喃)丙烯酰胺及其酯类衍生物26个的合成。动物筛选结果表明;化合物Ⅲ_(?)。,Ⅲ_6和Ⅲ_(13)对感染日本血吸虫小白鼠有明显的治疗作用。化合物Ⅱ_(?)有较明显的预防作用。     

硝基呋喃酰胺衍生物的合成及其抗血吸虫活性

目的合成含有酰胺基团的硝基呋喃衍生物,并进行小白鼠体外筛选和体内抗日本血吸虫活性测试。方法以四氢呋喃为溶剂,N,N'-二环己基碳二亚胺为缩合剂,5-硝基呋喃甲酸与1-羟基-苯并三氮唑(HOBt)缩合得到中间体,该中间体与胺缩合得到硝基呋喃酰胺类目标化合物。结果与结论合成了11个硝基呋喃酰胺类化合物,其中6个是未见文献报道的新化合物。抗日本血吸虫活性评价结果显示,有7个化合物对血吸虫具有一定的抑制效果,尤其是化合物N'-(2-吗啡啉基乙基)-5-硝基呋喃-2-酰肼(6k),抗虫效果最显著,可作为抗血吸虫的先导化合物做进一步研究。     

吡喹酮类似物的合成

本文合成了吡喹酮的3-位、6-位甲基取代衍生物(Ⅱ),2-位酰基、4-位内酰胺基还原产物(Ⅲ),以及C环开环化合物Ⅳ。并将合成的21个化合物进行了抗日本血吸虫的小鼠筛选,结果表明:3-位或6-位有甲基取代的化合物具有抗日本血吸虫活性,而当3-,6-位同时引入甲基,则活性大大下降,2-位酰基换成烃基或4-位内酰胺基还原成胺基均失去活性;部分C环开环化合物仍有活性,但较弱。     

血吸虫病化学预防药物4H—吡嗪并〔2,1—a〕异喹啉衍生物的合成

合成了３３个４Ｈ－吡嗪并〔２，１－α〕异喹啉衍生物。动物试验结果表明，其中７个化合物对日本血吸虫病具有治疗作用，５个化合物兼有预防和治疗作用。尤以２－〔４＇－（Ｎ，Ｎ－二乙基甘氨酰胺基）苯甲酰基〕－４－氧－１，２，３，６，７，１１ｂ－六氢－４Ｈ－吡嗪并〔２，１－α〕异喹啉为突出。它对刚钻入小鼠皮肤的血吸虫童虫及对成虫的杀灭作用与吡喹酮相仿，而且对１４ｄ的日本血吸虫童虫呈一定治疗作用。     

茜草科植物Palicourea condensata中新的抗HIV大环肽

前曾报道,茜草科植物P.condensataStandl.在抗HIV初步筛选中显示活性,并从中分得生物碱、氟乙酸和三萜类化合物。曾从该科其他植物中分得大环肽。作者从该植物有机提取物的水溶性部位中首次分离出1个新的大环肽palicourein。     

Fluoroacetic acid in guar gum

The toxicity of guar gum, derived from the Indian leguminous plant Cyamopsis tetragonolobus, is thought to be due to a globulin which can be denaturated and made non-toxic. Another very toxic compound, fluoroacetic acid, has been detected at a low level in raw samples of guar gum (0.07–1.42 μg fluoroacetic acid/g). A sample of a guar-gum pharmaceutical formulation contained only 0.08 ppm fluoroacetate. One exceptionally high value of 9.5μg/g was found in a guar-gum powder. The low concentrations of fluoroacetate found in guar gum dispel any considerations about possible health risks associated with fluoroacetate during the prolonged use of guar gum at the recommended doses.     

右旋肌醇的制备方法

目的 采用春雷霉素酸水解制备获得高纯度右旋肌醇的工艺方法研究.方法 采用春雷霉素原料通过三氟乙酸催化高温水解,除杂脱色,结晶获得右旋肌醇.结果 右旋肌醇外观、溶解度、灰分、及HPLC纯度等检测结果均达到合格标准,制备工艺快速可放大重复.结论 该方法原料廉价易得,制备快速、重复性好,可制备高纯度右旋肌醇.     

N-(4-乙氧羰基苯基)维生素甲酰胺与维生素甲酸衍生物的毒性比较

本文比较了我所合成的N-(4-乙氧羰基苯基)维生素甲酰胺(简称RI)及N-(4-羧酸苯基)维生素甲酰胺(简称RII)与维生素甲酸及其已知衍生物Ro10-9359、Ro 11-1430及Ro 4-3780的毒性。维生素甲酸、Ro10-9359及Ro11-1430可引起维生素甲过多症等毒性。Ro11-1430对精子有抑制作用。Ro4-3780对动物体重增长有影响。RII可导致肝组织损伤和脂肪变性,对精子亦有抑制作用。RI比维生素甲酸、Ro10-9359及Ro11-1430剂量高达4倍以上,比Ro4-3780剂量高33%,比RII剂量高1倍仍未见明显毒性。     

防癌药物的研究——维生素甲酸衍生物的合成

为寻找防癌药物,从改变维甲酸的结构、物化性质,以改变在体内的运转、分布和生物活性,达到提高疗效,降低毒性的目的,而合成了27个维甲酸酯和酰胺衍生物。部分化合物已进行预防致癌实验。结果证明,有些化合物有效,其中维甲酰(4-乙氧羰基苯胺)(1)的效果较好,毒性低,可能是一个有希望的防癌化合物。     

抗血吸虫病药鹤草酚类似物的合成

鹤草酚(Agrimophol)(Ⅰ)是从植物仙鹤草(Agrimonia pilosa Ledeb)根芽中分离出来的一种驱绦虫有效成分,王根法等发现它有抗血吸虫作用,但减虫率不高,胃肠道反应也较重。鹤草酚是间苯三酚的衍生物,分子中有角甲基,人工合成较复杂。我们企图改变其化学结构,使成为结构简单而又易于制备并有抗血吸虫活性而毒性低于鹤草酚的类似物。文     

Determination of sodium monofluoroacetate (compound 1080) in tissues and baits as its benzyl ester by reaction-capillary gas chromatography

A reaction-capillary gas-chromatographic procedure using photo-ionization (PID) or flame-ionization (FID) detection was developed for the determination of sodium monofluoroacetate (compound 1080), a pesticide, in tissues and baits. Fluoroacetic acid from tissue (1 g) and bait (10 g) extracts was first partitioned into ethyl acetate and then into 0.5 M benzyldimethylphenylammonium hydroxide. Benzylation was achieved by pyrolysis of the quaternary ammonium salt in the injection port. Chloroacetic acid was used as the internal standard. A linear relationship (r = 0.999) was observed between the peak area ratio of the substrate/internal standard and the fluoroacetic acid concentration. The detection limit for compound 1080 using the described analytical procedure, was 15 micrograms/kg with PID and 100 micrograms/kg with FID.     

Turbidimetric and HPLC assays for the determination of formulated lysozyme activity

In several studies lysozyme has been employed as a model protein to investigate the effects of formulation factors upon biological activity. The aim of this work was to develop and validate an HPLC technique to assay lysozyme and to compare the results with biological activity determined from a validated turbidimetric assay. The turbidimetric assay was based upon the lytic action of lysozyme on Micrococcus lysodeikticus cells, whilst the reverse-phase HPLC assay employed an acetonitrile gradient in 0.1% trifluoroacetic acid. The limits of detection and quantification were 3.84 and 6.24 microg mL(-1) for HPLC assay, whilst the corresponding values for turbidimetric assay were 1.94 and 3.86 microg mL(-1). The methods were used to monitor the loss of enzyme activity after heating. Lysozyme concentrations determined from HPLC peak height were found to correlate (r2 = 0.9963) with those obtained from turbidimetric assay.     

Synthesis of histidine-containing dipeptide affinity-labelling agents

Peptidyl diazomethyl ketones and fluoromethyl ketones containing histidine in the C-terminal position were synthesized to determine their properties as proteinase inactivators. These were examined chiefly with derivatives of Z-Ala-His. The protection of histidine during conversion of the C-terminal residue to the diazomethyl ketone required unblocking conditions which avoid acid due to the lability of this function. This was achievable with a Cbz-imidazole derivative since aminolysis provided deblocking without disturbance of the diazomethyl ketone function. In the case of the fluoromethyl ketone synthesis using fluoroacetic anhydride (Dakin-West procedure), the desired product could be isolated without ring blocking. The Z-Ala-His products showed enhanced selectivity for inactivation of cathepsin B over L when compared to analogous dipeptide inhibitors.     

The role of hydrolases in insecticide metabolism and the toxicological significance of the metabolites

The hydrolytic enzymes involved in insecticide metabolism are the phosphorotriester hydrolases, carboxylesterases, carboxylamidases and epoxide hydrolases. The phosphorotriester hydrolases (arylesterases and DFP-ases) catalyze the P-anhydride bond cleavage of the "leaving group", a major route of detoxication of organophosphates. Carboxylesterases hydrolyze the carboethoxy group of malathion and also have hydrolytic activity toward certain synthetic pyrethroids. Carboxylamidases are involved in the hydrolysis of amide-containing phosphorothionates, N-formyl metabolites and substituted fluoroacetamides. Epoxide hydrolases hydrate certain cyclodiene insecticides and are probably involved in the metabolism of some other insecticides. Overall, the hydrolysis of insecticides increases the polarity of the metabolites and decreases their biological activity.     

Comparative toxicity to mice of domoic acid and isodomoic acids A, B and C

Seafood in many parts of the world may become contaminated with high levels of domoic acid and domoic acid isomers, and such seafood has been shown to cause toxic effects in humans and in marine animals. Domoic acid itself has been held responsible for the observed effects, although the possible contribution of the isomers to toxicity has not been investigated. In the present study, the acute intraperitoneal toxicity of isodomoic acid C in mice was found to be lower than that of domoic acid. Furthermore, the severities of the behavioural changes induced by isodomoic acids A, B and C were all much lower than that of domoic acid itself, suggesting that these substances pose relatively little risk to human or animal health.