8-(N,N-二甲基-胺甲基)-黄芩苷对非白假丝酵母的抑菌作用

目的探索分析8-(N,N-二甲基-胺甲基)-黄芩苷抗非白假丝酵母的作用,拓宽其应用范围。方法将近平滑假丝酵母、克柔假丝酵母、光滑假丝酵母的标准菌株及临床菌株选为待试菌株,测定8-(N,N-二甲基-胺甲基)-黄芩苷、黄芩苷及伊曲康唑对待试菌株的抑菌圈直径。结果除伊曲康唑对部分待试菌株耐药外,3种药物对待试菌株存在一定的抗菌作用。8-(N,N-二甲基-胺甲基)-黄芩苷对近平滑假丝酵母标准菌株、近平滑假丝酵母临床菌株、克柔假丝酵母临床菌株的抑菌圈直径分别为(29.44±5.27)mm、28.00(25.00,30.00)mm、18.00(15.00,24.00)mm,大于黄芩苷;对光滑假丝酵母临床菌株的抑菌圈直径为25.00(20.00,28.00)mm,大于伊曲康唑(P<0.05)。其对光滑假丝酵母的标准菌株、临床菌株的抑菌圈直径分别为(25.56±4.64)mm、25.00(20.00,28.00)mm,小于黄芩苷;对克柔假丝酵母的标准菌株、临床菌株的抑菌圈直径分别为(18.89±3.33)mm、18.00(15.00,24.00)mm,小于伊曲康唑(P<0.05)。结论 8-(N,N-二甲基-胺甲基)-黄芩苷对近平滑假丝酵母标准菌株、近平滑假丝酵母临床菌株、克柔假丝酵母临床菌株的抗菌作用优于黄芩苷,对光滑假丝酵母临床菌株的抗菌作用优于伊曲康唑;其对光滑假丝酵母的标准菌株、临床菌株的抗菌作用弱于黄芩苷,对克柔假丝酵母的标准菌株、临床菌株的抗菌作用弱于伊曲康唑。     

尿中N,N-二甲基乙酰胺及其代谢物N-甲基乙酰胺的气相色谱测定法

目的:建立职业工人尿样中的N,N-二甲基乙酰胺(DMAC)及其代谢产物N-甲基乙酰胺(NMAC)的气相色谱测定方法。方法:尿样经冻融后离心,上清液加甲醇(1∶1,v/v)后用HP-INNOWAX毛细管柱分离,氢火焰离子化检测器(FID)对尿样进行检测,外标法定量。结果:DMAC和NMAC在0μg/ml～300.0μg/ml内呈线性关系;相关系数为0.9999;最低检出限分别为1.65μg/ml和2.90μg/ml;样品加标回收率分别为99.8%～100.4%和98.0%～99.9%。结论:该法操作简便、快速、准确、灵敏度高,适用于职业工人尿样中DMAC、NMAC的同时测定。     

N-(5-硝基吲唑-3-甲酰)苯丙氨酸钠的制备与乏氧增敏研究

目的 合成N-(5-硝基吲唑-3-甲酰)苯丙氨酸钠并考察其对Hela细胞和小鼠移植瘤模型的乏氧增敏作用。方法 缩合剂法合成N-(5-硝基吲唑-3-甲酰)苯丙氨酸钠,通过乏氧细胞模型和乏氧小鼠移植瘤模型评价其乏氧增敏活性。结果 合成了目标化合物并对结构进行了确证。细胞和移植瘤模型表明其具有一定的乏氧增敏活性。结论 N-(5-硝基吲唑-3-甲酰)苯丙氨酸钠具有良好的乏氧增敏活性,具有进一步研究价值。     

Comparative toxicity of the phytotoxins (8R,16R)-(-)-pyrenophorin and (5S,8R,13S,16R)-(-)-pyrenophorol on aquatic organisms

The acute toxicities of the fungal phytotoxins (8R,16R)-(−)-pyrenophorin and (5S,8R,13S,16R)-(−)-pyrenophorol on Vibrio fischeri, Oscillatoria perornata, Pseudokirchneriella subcapitata, Lemna minor and Artemia fransiscana were evaluated. (8R,16R)-(−)-pyrenophorin was more toxic than (5S,8R,13S,16R)-(−)-pyrenophorol to V. fischeri, O. perornata, L. minor and A. fransiscana. The highest acute toxicity of (8R,16R)-(−)-pyrenophorin was exhibited on V. fischeri (5 min median effective concentration of 3.57 M 10⁻⁵) whereas the corresponding value for (5S,8R,13S,16R)-(−)-pyrenophorol was 801 M 10⁻⁵. P. subcapitata exhibited a lack of sensitivity (median inhibitory concentration of >10 M 10⁻⁵) to both phytotoxins.     

Synthesis, characterization and antidiabetic properties of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium(IV)

A new oxovanadium(IV) chelate [VOL] (L: N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato) was synthesized and characterized by elemental analysis, conductivity and magnetic measurements, UV-vis, IR, EPR spectroscopy and mass spectrometry. The biochemical and immunohistochemical effects of the administration of the vanadium complex (VOL) into the pancreas of normal and streptozotocin-induced diabetic rats were profoundly investigated. The animals were randomly divided into four groups. Group I: control (intact) animals. Group II: control animals administered with VOL. Group III: STZ-induced diabetic animals. Group IV: STZ-induced diabetic animals administered with VOL. VOL was given to some of the experimental animals by gavage at a dose of 0.2mM/kg every day for 12 days. Blood samples were collected from animals, on 0 and 1, 6 and 12 days after STZ injection. On day 12, the pancreatic tissues were taken from the animals. The tissue sections were labelled with streptavidin biotin peroxidase technique for insulin. In the diabetic group, the blood glucose levels, aspartate and alanine transaminases, alkaline phosphatase activities were increased. But, in the diabetic+VOL groups, the blood glucose levels, aspartate and alanine transaminases, alkaline phosphatase activities were reduced. In the diabetic group, a decrease in the pancreatic glutathione levels, glutathione peroxidase and superoxide dismutase activities and an increase in the pancreatic lipid peroxidation level and catalase activities were observed. The administration of VOL to the diabetic rats reversed this diabetic effect due to its insulinomimetic effects. According to the immunohistochemical and biochemical results obtained, it was concluded that VOL can regenerate B cells of the pancreas in experimental diabetes and has an antidiabetic and protective effects on the pancreas.     

Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives

Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5c, 5g, 5j and 5n were found active in MES model, while 5o showed significant antiepileptic activity in scPTZ model. Further all these five compounds were administered orally to rats, 5c, 5g and 5n showed better activity than Phenytoin in oral route. Among these compounds 5c revealed protection in MES at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration respectively. This molecule provided also protection in the scPTZ at a dose of 300 mg/kg in both time intervals.     

New N6- or N(9)-hydroxyalkyl substituted 8-azaadenines or adenines as effective A1 adenosine receptor ligands

In this paper we describe synthesis and biological assays of some A(1) ligands more water-soluble than the effective, but very lipophilic, 8-azaadenines and adenines discovered in the past and obtained introducing on N(6) or N(9) substituent a hydroxy group. Five of the new N(6)-hydroxyalkyl- and N(6)-hydroxycycloalkyl-2-phenyl-9-benzyl-8-azaadenines showed very high affinity (Ki<40 nM) and selectivity for A(1) adenosine receptors. Among the 2-phenyl-9-(2-hydroxy-3-alkyl)-8-azaadenines or adenines prepared, the compounds with the higher A(1) affinity and selectivity resulted 2-phenyl-9-(2-hydroxy-3-propyl)-N(6)-cyclopentyl- and cyclohexyl-8-azaadenine with Ki 2.2+/-0.2 nM and 2.8+/-0.3 nM respectively. From the point of view of water-solubility, 2-phenyl-9-(2-hydroxy-3-propyl)-8-azaadenine was the most interesting compound, having a CLogP of 1.066991 and a water-solubility of 1.2 mg mL(-1).     

The anti-estrogenic effect of 4-chloro-1,2-diphenyl-1-(4-[2-(N,N-dimethylamino)ethoxy]phenyl)1-butene (Toremifene) on the endocrine regulation in breast cancer patients

In a combined phase I-II study the hormonal effects of Toremifene were investigated in 15-15 patients at two dose levels: 60 mg and 300 mg per os, daily. Serum estradiol, progesterone, testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, human growth hormone were monitored by radioimmunoassay and sexual hormone binding globulin by immunoradiometric assay prior to treatment and at the 2nd, 8th and 12th weeks. The influence of Toremifene upon the hypothalamo-hypophyseal axis was also controlled by a tirotropin releasing hormone functional test using 400 micrograms tirotropin releasing hormone injection iv. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and prolactin decreased proving the antiestrogenic activity of the drug. Sexual hormone binding globulin significantly (p less than 0.002) increased by week 12 at both doses, probably due to a direct effect of Toremifene upon the liver. The increase in sexual hormone binding globulin suggests the partial estrogenic effect of the drug. The tirotropin releasing hormone induced prolactin release was also suppressed. On the basis of hormonal changes and the clinical response of patients 60 mg of Toremifene proved to be as effective as 300 mg.     

右旋反式氯丙炔菊酯的合成及其药效研究

目的研制一种新型卫生杀虫剂--右旋反式氯丙炔菊酯.方法采用右旋反式DV菊酸与S-炔丙醇酮为原料,经化学拆分、酰氯化及酯化等反应合成右旋反式氯丙炔菊酯,并采用GB/T13917.1-1992和GB/T17322.2-1998标准方法测定了对致倦库蚊和德国小蠊的药效.结果右旋反式氯丙炔菊酯对致倦库蚊及德国小蠊的KT50值分别为8.5 min和3.46min.结论右旋反式氯丙炔菊酯对蚊虫和蟑螂等害虫具有良好的击倒作用和杀灭能力,可以作为一种新型卫生杀虫剂加以推广和应用.