Alpha1- and alpha2-adrenoreceptor antagonist profiles of 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles

A series of pharmacologically interesting 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles, compounds 1-27, were synthesized (Scheme) and subjected to various biological studies to identify structure-activity relationships (SAR). The new compounds were found to exhibit good non-selective binding affinity towards the alpha1-adrenoreceptor (Table 1). In several cases, high functional antagonism was observed towards the alpha1A-, alpha1B-, and alpha1D-adrenoreceptor subtypes (Table 2). The selectivity for these three subtypes was comparable with or superior to that displayed by the standard drug prazosin. The most-common selectivity rank order was alpha1D > alpha1B > alpha1A, followed by alpha1B > alpha1D > alpha1A. In functional experiments, antagonism towards the alpha2-adrenoreceptor was generally low; however, a few compounds were endowed with significant antagonist properties (pA2 values of up to 7.87).     

New clerodane diterpenoids from the aerial parts of Pulicaria wightiana

Two new ent-clerodane-type diterpenoids, compounds 1 and 2, were isolated from the aerial parts of Pulicaria wightiana, together with three known constituents. Their structures were established based on spectroscopic data, and their antibacterial activities were evaluated (Table 2).     

油菜甾醇内酯类化合物结构与活性的相关性

比较了19种油菜甾醇内酯类似物和有关甾体化合物在水稻叶片倾斜及萝卜幼苗生长试验中的生物活性。表油菜甾醇内酯(24—Epi—BR)在两个系统中都具有很强的生物活性。C_2位失去羟基(香蒲甾醇)仅在水稻试验中有高活性,改变C_22位侧链结构(2α,3α双羟基—6—酮—23,24—双失碳—β—高-5α—胆烷酸甲酯)在萝卜试验中仍有活性。     

Phenolic antioxidants from the whole plant of Phyllanthus urinaria

The 1,1-diphenyl-2-picrydydrazyl (DPPH) assay on the extract of Phyllanthus urinaria L. (Euphorbiaceae) displayed considerable radical-scavenging activity (SC50 = 14.3 microg/ml). Further bioassay-guided purification of the extract led to the isolation of a series of 15 phenolic compounds, including the ellagitannins 1-7, the flavonoids 8-10, and the simple hydroxylated (or glycosylated) aromatic acids 11-15. Their structures were identified by spectroscopic analyses and comparison with authentic samples or literature data. The structure of repandinin B (1) was for the first time fully assigned by 1D- and 2D-NMR experiments. The phenolic compounds 1, 3, 4, 6, 9, 11, and 15 have not been isolated before from the title plant. The antioxidant activities and mushroom-tyrosinase-inhibitory activities of all compounds were determined by DPPH-radical-scavenging and mushroom-tyrosinase-inhibitory assays (Table 2).     

Phenoxy-Acid-Induced Renal Changes in the Chicken

Forty-five day-old broiler chicks were equally divided into 3 groups, 2 being fed 2,4-D and 2,4,5-T, respectively, from the fifth day of life for up to 7 months, at 1,000 p.p.m. in the drinking water, and the third serving as a control. From 8 weeks of age 2 of the control animals were fed 2,4-D at the same rate for 7 months. Seven of the treated animals died, or were killed in a moribund state, during the experiment (Table 1), the survivors showing only slight signs of poisoning such as reduced mobility and food and water intakes. Animals were sacrificed after varying time intervals (Table 1). The tissue distribution patterns of 2,4-D and 2,4,5-T, as determined in selected tissues of a few of the animals (Table 2), were similar to that observed earlier with 2,4-D. Both compounds produced qualitatively similar morphological effects, although the action of 2,4,5-T apparently was somewhat more intense. The predominant necropsy finding was kidney enlargement (Table 1) due to hypertrophy of the proximal convoluted tubular epithelium (Fig. 1). Electron-microscopically, increased numbers of mitochondria were demonstrated in the tubular cells, with variations in mitochondrial size, shape and structure (Figs. 4–7). The number of micro-bodies was also definitely increased (Figs. 2 and 4). In the nuclei nuclear bodies were observed (Figs. 2 and 3). The significance of the findings is discussed.     

Synthesis of novel 3-(alkylcarbamoyl)-2-aryl-1,2-dihydro-6,7-(methylenedioxy)-3H-quinazolin-4-ones as anticonvulsant agents

A series of 3-(alkylcarbamoyl)-2-aryl-1,2-dihydro-6,7-(methylenedioxy)-3H-quinazolin-4-ones, compounds 3-6, were synthesized, and screened as anticonvulsant agents in DBA/2 mice against sound-induced seizure (Table). The new compounds were found to display anticonvulsant properties inferior to those of the known dehydro congeners 1 and 2. The binding affinities of 1-6 at the AMPA and NMDA receptors were also evaluated.     

Isolation, DNA topoisomerase-II inhibition, and cytotoxicity of three new terpenoids from the bark of Macaranga tanarius

One new pimarane-type diterpenoid (1) and two new taraxerane-based triterpenoids (2 and 3) were isolated from the bark of Macaranga tanarius, along with seven known compounds. Their structures were identified by spectroscopic methods including NMR and MS analyses. Compounds 1-5 were tested for their in vitro inhibition of DNA topoisomerase II, as well as for their cytotoxicities against human lung carcinoma A549 cells (Table 3). The triterpenoids 2-5 showed strong activities in both assays, but the diterpenoid 1 was only moderately active.     

New racemosol derivatives as potent cyclooxygenase (COX) inhibitors

Racemosol (1) and 10-O-demethylracemosol (2), natural products from Bauhinia malabarica Roxb., exhibit potent in vitro anti-inflammatory activities against cyclooxygenase-1 and -2 (COX-1 and -2) enzymes. To investigate the structure-activity relationship (SAR) of these molecules, we prepared and fully characterized 17 derivatives by functionalizing one, two, or all three OH group(s) of 2 (Scheme). Both the size and polarity of the substituents as well as the substitution pattern in compounds 3a-q were found to be critical for anti-inflammatory activity. The orientation of the drugs and their mode of binding were studied by molecular docking based on the known 3D structure of the complex between COX-2 and the drug SC-558. Whereas the monoacetoxy derivative 3h exhibited an equally potent inhibitory activity towards both COX-1 and -2 (Table 1), its diacetoxy congener 3i was slightly more selective toward COX-2. In vivo anti-inflammatory tests showed that 3i and 2 are slightly more active than the reference compound phenylbutazone (Table 2).     

A homo-isoflavonoid and a cytotoxic saponin from Dracaena draco

Two new compounds, dracol (= (3R)-2,3-dihydro-3,5-dihydroxy-7-methoxy-3-[(4-methoxyphenyl)methyl]-8-methyl-4H-[1]benzopyran-4-one; 1) and icodeside (= (1beta,3beta,23S,24S)-3,23-dihydroxy-1-{[2-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-alpha-L-arabinopyranosyl]oxy}spirosta-5,25(27)-dien-24-yl alpha-L-arabinopyranoside; 2), were isolated from the EtOH extract of the leaves of Dracaena draco, together with 17 known constituents. The structures of 1 and 2 were elucidated by in-depth spectroscopic analysis, and those of the known compounds were identified by comparison of their NMR and MS data with those reported in the literature. Icodeside (2) showed moderate cytotoxicity against human HL-60 and A-431 cells (Table 3).     

Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains - including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini - afforded ten different metabolites, compounds 2-11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane-based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more-potent respiratory-burst inhibitory activity than the substrate 1 in a neutrophil-based cellular assay (Table 3).     

Structure elucidation and antibacterial activity of new fungal metabolites of sclareol

The transformation of the antibacterial diterpene sclareol (1) by two different fungal strains was investigated (Scheme). In the presence of Rhizopus stolonifer, (3beta)-3-hydroxysclareol (2), 18-hydroxysclareol (3), (6alpha)-6,18-dihydroxysclareol (4), and (11S)-11,18-dihydroxysclareol (5) were formed. Fermentation of 1 with Fusarium lini afforded (1beta)-1-hydroxysclareol (6) and (12S)-12-hydroxysclareol (7). Compounds 4-7 were identified as new compounds, and some of them were active against Bacillus subtilis (Table 3).     

T-DNA插入产生的水稻迟抽穗突变体的遗传分析

在筛选和鉴定水稻T-DNA插入纯合体的过程中,观察到一个迟抽穗的突变体.对该突变体进行遗传分析的结果表明,分离群体后代中出现正常抽穗、迟抽穗和特迟抽穗3种类型,分离比率为1:2:1,符合一对基因的不完全显性遗传;对突变体及其后代分离群体做Basta抗性检测及PCR分子检测,证实该突变体是由T-DNA插入所引起的,突变性状与T-DNA共分离.该材料可用于插入座位的基因克隆.     

Antiphytovirale Verbindungen mit nichtzyklischer Azin Struktur

Antiphytoviral compounds with noncyclic azine structutre The antiphytoviral activities of variously substituted compounds with noncylic azine structures have been studied f a total of 90 tested compunds 42 had the effect of more or less strong inhibiting the concentration of potato virus X (PVX) in inoculated and / or secondarily infected leaves of Nicotiana tabacum L. cv Samsun (Table.1) An effect on the virion of PVX in vitro couldn't be observed (Table.2) Thus the substances may interact with the virus replication. Some of them also reduced the number of local lesions caused by tabacco mosaic virus on leaves of Nicotiana glutinosa L. (Table-3) Several Compounds proved exellent synergists of 2,4- dioxohexahydro- 1,3,5- triazine (DHT = 5 azadihydrouracil; Table 4) Pyridine- 3- aldehyde S ethyl isothiosemicarbazone and the Cu complex of 1- ethyl-isatine S- ethyl isothisosemicarbazone when used in combination with 2,4 dioxohexahydro- 1,3,5, triazine, greatly increased the mass of potato tubers produced from plantlets grown up from patato eye cutting as compared with the indentical control Simultaneously the mentioned substances reduced the number of symptom bearing eye cutting plants Quinoline 2- aldehyde- N- oxide S- allyl-isothiosemicarbazone had the effect of very greatly reducing the number of symptom-bearing plants without substantially influencing the mass of tubers (Table 5). Thus some compounds with noncyclic azine structure especially when used in combinitation with DHT, may be of high interest for practical application Comparing the structures of compounds with noncyclic azine structure active against plant or human viruses it should be noted that antiphytoviral compounds active in these two different virus host systems often are closely related structurally.     

Photocytotoxic pheophorbide-related compounds from Aglaonema simplex

In our screening program for new photosensitizers from the Malaysian biodiversity, we found five pheophorbide-related compounds from the leaves and stems of Aglaonema simplex. Detailed spectroscopic analyses showed that compounds 1-3 and 5 are pheophorbide and hydroxy pheophorbide derivatives of chlorophyll a and b. Compound 4, identified as 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester, was isolated for the first time from the Araceae family. An MTT-based short-term survival assay showed that all five compounds exhibit moderate-to-strong photocytotoxic activities towards human leukemia (HL60) and two oral squamous carcinoma cell lines (HSC-2 and HSC-3). Compounds 4 and 5 showed the strongest photocytotoxicities, with IC(50) values of 0.30-0.41 muM (Table 2). Compounds 1-3 with Et chains at C(17(3)) were less photocytotoxic than the parent pheophorbide a (5).     

The influence of living plants on mineralization and immobilization of nitrogen

Summary Changes in the pattern of distribution of the nitrogen of the soil and seedling grass plants have been investigated when the grass plants were grown in pots of sandy soil, from a pasture, at pH 5.7. Net mineralization of soil nitrogen was not observed during an experimental period of one month in the absence of added nitrogenous fertilizer (Table 2). Addition of labeled nitrogen (as ammonium sulphate) to the soil at the beginning of the experimental period resulted in a negative net mineralization during this period (Table 4b). When none of the fertilizer nitrogen remained in its original form in the soil it was found that approximately 12 per cent of the labeled nitrogen had been immobilized in soil organic compounds. Clipping of the grass at this date was followed by a decrease in the amount of labeled soil organic nitrogen, indicating that mineralization was not depressed by living plants. The application of unlabeled ammonium sulphate subsequent to the utilization of the labeled nitrogen did not decrease the amount of immobilized labeled nitrogen in the soil organic matter, as would be expected if the organic nitrogen compounds of the soil had been decomposed to ammonia. This was thought to be due to the fact that decomposition of organic nitrogen compounds in permanent grassland results in the production of peptides, amino acids etc. which are utilized by microorganisms without deamination taking place. In pots with ageing grass plants, labeled organic nitrogen compounds were found to be translocated from the grass shoots to the soil (Table 7). Net mineralization of soil organic nitrogen was positive in the contents of pots containing killed root systems (Table 3b). About 8 per cent of the labeled nitrogen added to the contents of such pots, in the form of ammonium sulphate, was found to be present in soil organic nitrogen compounds approximately 4 weeks after application, while a total of about twice this amount of soil organic nitrogen was mineralized during that period. From the results obtained in this investigation, it is concluded that the constant presence of living plants is responsible for the accumulation of nitrogen in organic compounds in permanent grassland. No evidence was obtained that the decomposition of such compounds in the soil is inhibited by living plants.     

A pair of novel cytotoxic polyprenylated xanthone epimers from gamboges

Two new polyprenylated xanthone epimers were isolated from gamboges of Garcinia hanburyi, and identified by detailed spectroscopic analysis as 30-hydroxygambogic acid (2a) and its (2S)-epimer 30-hydroxyepigambogic acid (2b). Both compounds exhibited significant cytotoxicities against the human leukemia K562/S and the corresponding doxorubicin-resistant K562/R cell lines (Table 2).     

性激素对大鼠诱发肝癌中胎盘型谷胱甘肽S-转移酶(GST-P)表达的影响

本实验利用Solt-Farber顺序诱发大鼠肝癌,观察肝组织中GST活性及GST-P含量在化学诱癌中的变化,并观察性激素对大鼠化学诱发肝癌的早期病变中GST-P表达的作用。结果显示无论是GST活性或GST-P的含量,在诱癌至第三周开始升高,第五周升至最高。利用此模式,选择诱癌至第五周,免疫组化法检测各种处理后肝组织中GST-P的表达。发现睾丸假切除的雄性大鼠经化学诱癌后,肝中有高的GST-P表达,睾丸假切除的雄性大鼠诱癌合并雌二醇处理,明显降低肝组织GST-P阳性灶的面积和数量;合并睾丸酮处理,虽减少GST-P阳性灶的面积,但其数量略有升高。与睾丸假切除后诱癌的雄性大鼠相比,切除睾丸的大鼠经诱癌,有更低的GST-P阳性灶的面积;睾丸切除合并雌二醇处理,GST-P阳性灶的面积进一步降低。与仅化学诱癌的卵巢假切除雌性大鼠比,卵巢切除鼠诱癌后,GST-P阳性灶的面积稍有增加;对卵巢切除合用睾丸酮的大鼠诱癌,阳性灶的面积进一部增加。无论性腺切除与否,雄性大鼠比雌性大鼠有更高的GST-P表达。这些结果提示雌激素可抑制而雄激素则可促进化学诱癌大鼠肝中GST-P的表达。这一结果可能与临床上男性较女性易患肝癌有关。     

蓝藻(Anabaena 7120)的光合放氢和参与放氢的酶

蓝藻Anabaena 7120放氢是一个依赖于光的过程,暗中几乎测不出放氢活性。静置方式培养的蓝藻预先进行强化培养是测得高放氢活性的重要条件。年轻的蓝藻放氢活性比年老的高。氯化铵和一系列光合作用抑制剂对蓝藻放氢有抑制作用,弱光加剧氯化铵对放氢的抑制。在弱光加光合抑制剂的条件下,受氯化铵抑制的放氢活性恢复速度比强光下慢。CO_2、N_2、NaN_3和KNO_3与放氢竞争电子而抑制蓝藻的放氢。C_2H_2促进蓝藻放氢,CO则抑制放氢,C_2H_2和CO一起加入时,放氢受到的促进显著比单加C_2H_2的大。经分子氢预处理过的蓝藻,其放氢活性在光下可以得到明显的促进。     

细叶亚菊挥发油中抑制垂穗披碱草的化合物的分离与鉴定

用气相色谱－质谱联机光谱分析法,分离、提纯,鉴定细叶亚菊挥发油中抑制垂穗披碱草生长的化合物４９种,有α－蒎烯、莰烯、蒈品－３－烯、桉叶油精、胡薄荷酮、樟脑、萜品烯－４－醇和乙酸菊烯酸酯８种主要化合物,而占总细对亚菊挥发油的８２．８０％。其中樟脑最多,胡薄荷酮和桉对油精为次。     

ABA和乙烯在草莓采后成熟衰老中的作用

随着草莓果实采后成熟衰老,ABA和乙烯生成迅速增长,乙烯累积与果实的变质腐烂程度呈正相关。ABA处理能增高纤维素酶活性和呼吸,而GA有抑制作用。ABA能促进乙烯、ACC生成,对MACC则无影响。GA_3抑制乙烯、ACC生成,促进MACC积累。CO_2对草莓有良好保鲜效果,并有效地抑制ABA和乙烯生成,低温下效果更为显著。