碘伏和异噻唑啉酮对球形棕囊藻去除的研究

研究了碘伏和异噻唑啉酮除藻剂对球形棕囊藻赤潮生物的灭杀和控制作用,结果表明,单独使用时,碘伏的最低有效浓度为30mg.L^-1,异噻唑啉酮最低有效浓度为0.30mg.L^-1,当两者复配时有协同作用,可提高它们的杀藻能力,碘伏与异噻唑啉酮浓度比为1.0:0.15时除藻效果最佳。     

异噻唑酮用作循环冷却水杀菌灭藻剂的研究

本试验采用杯碟法、试管稀释法和显微直接计数法测试异噻唑酮对常见菌藻的抑杀效果,并用该药剂对循环冷却水主要危害菌——硫酸盐还原菌,铁细菌和形成粘液的异养菌进行室内静态杀菌试验。结果表明,其杀菌灭藻效果优于目前常用的工业杀菌剂,投药量10ppm,对水中主要危害菌的杀灭率达到99%以上。     

6-甲氧基-2-苯并唑啉酮(MBOA)分布不均匀是引起玉米胚芽鞘向光性运动的主要原因

采用高效液相色谱分析等方法,对玉米（ＺｅａｍａｙｓＬ．）胚芽鞘在单侧蓝光作用下产生的生物活性物质进行分析发现：１．在单侧蓝光作用下,胚芽鞘向光侧的生长抑制物质６甲氧基２苯并唑啉酮（ＭＢＯＡ）含量比背光侧多１．５倍。２．向光性刺激后,胚芽鞘向光侧和背光侧生长素的含量没有出现明显的差异。３．于胚芽鞘一侧外施ＭＢＯＡ及其类似物５,６ｄｉｍｅｔｈｏｘｙ２ｂｅｎｚｏｘａｚｏｌｉｎｏｎｅ（ＤＭＢＯＡ）和２ｃｈｌｏｒｏ５,６ｄｉｍｅｔｈｏｘｙ２ｂｅｎｚｏｘａｚｏｌｉｎｏｎｅ（ＣｌＤＭＢＯＡ）等抑制物质,均使胚芽鞘产生弯曲生长,表明引起玉米胚芽鞘向光性运动的直接原因是ＭＢＯＡ分布不均匀。     

异噻唑啉酮类杀菌剂的应用研究

本文主要阐述了异噻唑啉酮类杀菌剂的结构种类和特性,工业上的应用以及杀菌机理、抗药性等方面的研究进展以及在工农业和医药方面的应用进展。     

苯并(a)芘对鲫鱼肝脏EROD活性的影响

研究了典型多环芳烃类有机污染物苯并(a)芘(BaP)对鲫鱼(Carassius auratus)肝脏7-乙氧基-3-异吩唑酮-脱乙基酶(EROD)活性的影响。结果表明,注射后96 h,10和100 mg.kg-1处理组肝脏EROD活性被明显诱导,分别为对照组的2.3(P<0.05)和3.1倍(P<0.01)。肝脏EROD活性随着时间延长继续升高,至注射后14 d,1 mg.kg-1处理组鲫鱼肝脏EROD活性为对照的3.0倍(P<0.001),而100 mg.kg-1处理组则高达5.8倍(P<0.001)。鲫鱼肝脏EROD活性可作为反映BaP暴露水平的生物标志物。BaP对鲫鱼的最低效应浓度为1 mg.kg-1(鱼体重)。     

铜绿假单胞菌一氧化氮还原酶编码基因norD的生物学功能研究

一氧化氮还原酶(Nitric oxide reductase,NOR)是反硝化过程中一个非常重要的催化酶,本文通过同源重组的方法敲除铜绿假单胞菌中norD基因,并研究该基因敲除后菌株ΔnorD在好氧条件下的表型变化。研究结果表明,与野生菌株和回补菌株相比,ΔnorD对BIT的抗性增强。同时在BIT作用下,ΔnorD泳动能力减弱、绿脓菌素的合成能力降低,但norD基因不是BIT唯一的作用位点。上述结果明确了好氧条件下norD基因的部分功能,为更好的利用反硝化过程奠定基础。     

海洋真菌Aspergillus niger XJJ-3中萘并吡喃酮类化合物结构及生物活性

【背景】萘并吡喃酮类化合物生物活性多样,是真菌Aspergillusniger中特征次生代谢产物。【目的】研究分离自海洋滩涂土壤的真菌Aspergillus niger XJJ-3中萘并吡喃酮类化合物结构及其抗菌和卤虫致死活性。【方法】以TLC分析为导向,综合运用多种色谱和光谱方法分离和鉴定萘并吡喃酮类化合物。采用微量稀释法测试化合物的抗菌和卤虫致死活性。【结果】从真菌A.niger大米发酵产物中共分离得到6个萘并吡喃酮类化合物,鉴定为RubrofusarinB(1)、Flavasperone (2)、Aurasperone A (3)、Asperpyrones C (4)、Asperpyrones B (5)和Fonsecinone A (6)。抗菌活性实验结果表明,化合物1-6对致病菌S. aureus ATCC33591、29213、E. faecium ATCC35667和V.parahemolyticus表现出不同程度的抑制活性,其中化合物2和4对S.aureus ATCC33591表现出较强抑制活性(MIC分别为43.7μmol/L和21.9μmol/L),化合物3对E.faecium ATCC35667抑制活性较强(MIC为21.9μmol/L)。卤虫致死活性实验结果表明,化合物1-6均表现出一定的卤虫致死活性,其中化合物2和3活性显著(LD50分别为35.0μmol/L和8.8μmol/L)。【结论】菌株XJJ-3可产生结构丰富的萘并吡喃酮类化合物,化合物1-6存在不同程度的抗菌和卤虫致死活性,该研究可为抗菌和细胞毒类药物的研发提供参考。     

体外诊断试剂防腐剂的选择策略

对体外诊断试剂中防腐剂的作用机理及选择原则进行了阐述,并对目前常用的防腐剂如叠氮钠、庆大霉素、硫柳汞、异噻唑啉酮类等的性能进行了比较,为体外诊断试剂的研究开发及生产中防腐剂的使用提供有益指导。     

二氢呋喃喹啉酮类化合物的抑菌效果

为了解二氢呋喃喹啉酮类化合物对四种细菌的抑制作用,选用大肠杆菌,金色葡萄球菌,绿脓杆菌,枯草杆菌作为测试菌;选用牛肉膏蛋白胨作为培养基;以化学合成的二氢呋喃喹啉酮化合物a～f为测试对象,采用抑菌圈试验测定样品抗菌活性,并根据所得抑菌率求得MIC50值。结果表明:对于大肠杆菌,金色葡萄球菌,枯草杆菌,六个化合物的抑菌效果均一般。但是化合物f(含甲氧基)对于绿脓杆菌的抑菌效果尤其出色,远高于对大肠杆菌、金葡杆菌、枯草杆菌的抑菌效果,具有明显的选择性。     

杀菌剂苯并异噻唑啉酮对斑马鱼胚胎的急性毒性和氧化应激效应研究

苯并异噻唑啉酮(Benzisothiazolin,BIT)是一种广泛使用的工业防腐剂,在水体中分布较广,对水生生物特别是对鱼类存在潜在威胁。本研究以斑马鱼为受试生物,通过96 h急性暴露实验,氧化应激效应检测和相关基因表达量的分析,研究BIT对斑马鱼胚胎的发育毒性和氧化损伤。结果表明BIT对受精后51 h(51 hours post-fertilization,51 hpf)斑马鱼胚胎孵化具有强烈抑制作用,能导致胚胎畸形,96 h半致死浓度(96 h half lethal concentration,96h-LC50)为3.65 mg/L,96 h半数致畸浓度(96 h half teratogenic concentration,96 h-TC50)为1.31 mg/L。氧化应激相关酶(SOD,CAT,GST)的活性都受到了不同程度的影响,抗氧化相关基因(Mn-sod,cat,gstp-2,nqo-1,cox-1和ucp-2)的表达量也受到了干扰,这些结果说明机体受到了严重的氧化损伤。细胞凋亡相关基因(bcl-2和bax)的表达模式也向着促进凋亡的方向发生改变,表明氧化损伤导致了细胞凋亡。BIT对斑马鱼胚胎具有很高的发育毒性,能造成机体氧化损伤,最终导致胚胎死亡。本实验结果可为BIT在环境中的风险管理提供科学依据。     

Synthesis and biological activity of novel thiazolidin-4-ones with a carbohydrate moiety

Some novel 2-aryl-3-[5-deoxy-1,2-O-isopropylidene-α-d-xylofuranose-5-C-yl] thiazolidin-4-ones were synthesized by the three-component condensation of an amino sugar 1, an aromatic aldehyde 2, and mercaptoacetic acid 3 in the presence of DCC and DMAP at room temperature. Two diastereoisomers 4 and 5 were afforded as the main products in totally isolated yields of 25.4-70%. The reaction was carried out with almost no observed stereoselectivity except in the case of 2c, which showed a moderate stereoselectivity. The structures of the new compounds were determined by NMR spectroscopy and mass spectrometry (MS), and the configuration of the newly generated chiral carbon (C-2) in the thiazolidin-4-one ring was tentatively assigned based on the X-ray crystallographic structure of 5d and the comparison of their corresponding NMR signals. The antitumor (human cervical cancer cells) activity and the inhibition against the glycosidases (α-glucosidase, β-glucosidase, α-amylase) have been evaluated for the new compounds, some of which exhibited antitumor activity.     

Synthesis and biological evaluation of anti-Toxoplasma gondii activity of a novel scaffold of thiazolidinone derivatives

We designed and synthesised novel N-substituted 1,3-thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii efficacy. This scaffold was functionalised both at the N1-hydrazine portion with three structurally different moieties and at the lactam nitrogen with substituted benzyl groups selected on the basis of our previous structure-activity relationships studies. Using three different assay methods, the compounds were assessed in vitro to determine both the levels of efficacy against the tachyzoites of T. gondii (IC₅₀?=?5–148?μM), as well as any evidence of cytotoxicity towards human host cells (TD₅₀?=?68 to ≥320?μM). Results revealed that ferrocene-based thiazolidinones can possess potent anti-tachyzoite activity (TI =2–64).     

Synthesis and biological effects of aromatic analogs of abscisic acid

Thirty six different 3-methyl-5-aryl-2,4-pentadienoic acids and esters were synthesized using the Reformatsky and Wittig reactions. The different geometrical isomers were conveniently separated by the dry column technique. Assignment of configuration of the pentadienoic side chain was based on NMR and UV properties. The biological activities of the aromatic analogs of ABA were determined in four bioassays. Most of the analogs were less active than the natural hormone. Only 3-methyl-5-p-chlorophenyl Δ²-trans, Δ⁴-trans-pentadienoic acid exhibited high ABA-like activity in all four bioassays.     

Synthesis and biological activity of pyridopyridazin-6-one p38 MAP kinase inhibitors. Part 1

The development and synthesis of potent p38α MAP kinase inhibitors containing a pyridazinone platform is described. Evolution of the p38α selective pyridopyridazin-6-one series from the p38α/β dual inhibitor 2H-quinolizin-2-one series will be discussed in full detail.     

Synthesis and biological evaluation of some novel triazol-3-ones as antimicrobial agents

A new series of triazol-3-one derivatives bearing 4-methyl-4H-thieno[3',2': 5,6]thiopyrano[4,3-d][1,3]thiazolyl or 4-(thiophene-3-yl) thiazolyl moiety at 4-position and alkyl substitution at 2-position are synthesized. All the synthesized compounds are characterized by elemental analysis, IR, (1)H NMR, (13)C NMR, and mass spectral data. The newly synthesized compounds are screened for antifungal and antibacterial activities.     

Synthesis and biological activity of homoarginine-containing opioid peptides.

Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{omega,omega'-[Z(2Br)]2}-OH and Boc-Har{omega,omega'-[Z(2Cl)]2}-OH, were prepared by guanidinylation of Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)-OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide-resin was guanidinylated with N,N'-[Z(2Br)]2- or N,N'-[Z(2Cl)]2-S-methylisourea. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin-like enzymes.     

Synthesis of readily available fluorophenylalanine derivatives and investigation of their biological activity

A series of thirty novel N-acetylated fluorophenylalanine-based aromatic amides and esters was synthesized using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide or phosphorus trichloride in pyridine. They were characterized by spectral methods and screened against various microbes (Mycobacterium tuberculosis, non-tuberculous mycobacteria, other bacteria, fungi), for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and cytotoxicity. All amino acids derivatives revealed a moderate inhibition of both cholinesterases with IC₅₀ values for AChE and BChE of 57.88–130.75 µM and 8.25–289.0 µM, respectively. Some derivatives were comparable or superior to rivastigmine, an established drug. Phenyl 2-acetamido-3-(4-fluorophenyl)propanoate was identified as the selective and most potent inhibitor of BChE. The esterification and amidation of parent acids led to an improved BChE inhibition. The esters are better inhibitors of BChE than the amides. The introduction of NO₂ and CH₃ groups into aniline ring and CF₃ moiety in phenol is translated into lower IC₅₀ values. Seven compounds showed selectivity index higher than 10 for at least one cholinesterase. Especially the esters exhibited a mild activity against Gram-positive bacteria, mycobacteria and several fungal strains with minimum inhibitory concentrations starting from 125 µM. The highest susceptibility was recorded for Trichophyton mentagrophytes fungus.     

Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c

A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1–3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms α and γ. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity.     

Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates

The development of novel antimicrobial drugs represents a cutting edge research topic. In this study, 20 salicylanilide N,N-disubstituted carbamates and thiocarbamates were designed, synthesised and characterised by IR, ¹H NMR and ¹³C NMR. The compounds were evaluated in vitro as potential antimicrobial agents against Mycobacterium tuberculosis and nontuberculous mycobacteria (Mycobacterium avium and Mycobacterium kansasii) as well as against eight bacterial and fungal strains. Additionally, we investigated the inhibitory effect of these compounds on mycobacterial isocitrate lyase and cellular toxicity. The minimum inhibitory concentrations (MICs) against mycobacteria were from 4 μM for thiocarbamates and from 16 μM for carbamates. Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, were inhibited with MICs from 0.49 μM by thiocarbamates, whilst Gram-negative bacteria and most of the fungi did not display any significant susceptibility. All (thio)carbamates mildly inhibited isocitrate lyase (up to 22%) at a concentration of 10 μM. The (thio)carbamoylation of the parent salicylanilides led to considerably decreased cytotoxicity and thus improved the selectivity indices (up to 175). These values indicate that some derivatives are attractive candidates for future research.