Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore

A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides.     

Orally active 1,2,4-trioxepanes: synthesis and antimalarial activity of a series of 7-arylvinyl-1,2,4-trioxepanes against multidrug-resistant Plasmodium yoelii in Swiss mice

7-Arylvinyl-1,2,4-trioxepanes 7a-d, 8a-d, 9a-d, 10a-d, 11a-c, and 12a-c, prepared by photooxygenation of homoallylic alcohols 5a-d, were evaluated against multi-drug resistant Plasmodium yoelii nigeriensis in Swiss mice by oral and intramuscular routes. Trioxepane 11c, the most active compound of the series, showed more than 98% suppression of parsitaemia at 96 mg/kg by both oral and intramuscular routes. This is the first report on in vivo active 1,2,4-trioxepanes.     

New functionalized 1,2,4-trioxepanes: synthesis and antimalarial activity against multi-drug resistant P. yoelii in mice

A series of new amino functionalized 1,2,4-trioxepanes 8-16 and ester functionalized 1,2,4-trioxepanes 17-19 have been synthesized and evaluated against multi-drug resistant Plasmodium yoelii in Swiss mice. Amino functionalized trioxepanes 14, the most active compound of the series, showed 100% clearance of parasitaemia by oral route on day 4 and 75% protection to the treated mice beyond day 28.     

Determination of omeprazole via fluorescence-quenching methodology; application to content uniformity testing

A new, proven, economical spectrofluorimetric approach has been used to determine the proton pump inhibitor omeprazole (OMP). This innovative technique is based on the ability of OMP to quench the native fluorescence of the mercurochrome dye in an acidic (pH 3.6) solution. Because it was discovered that quenching is proportional to the drug concentration, this dye was used as a sensor for OMP detection. The fluorescence intensity was measured at 518/540 nm, and its linear response ranged from 0.2–10.0 μg/mL with a linear coefficient of 0.9999. The computation yielded a limit of quantification (LOQ) of 0.20 μg/mL and a limit of detection (LOD) of 0.07 μg/mL. Every circumstance and element impacting the reaction product was examined in detail. Pharmacopeial standards carried out the validation. The approved method investigated several commercial preparations and formulations, and the results were favorably compared with those provided by a reference method. According to United States Pharmacopeia (USP) rules, content consistency for two distinct formulations was evaluated.     

Synthesis of glycosyl-triazole linked 1,2,4-oxadiazoles

The synthesis of four different types of oxadiazoles containing a terminal acetylenic group is described. Reaction of these oxadiazoles with various azidoglycosides via a copper-catalyzed [3+2] cycloaddition ('click chemistry') afforded the corresponding glycosyl-triazole linked 1,2,4-oxadiazoles in good yields.     

Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology

a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel™ resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself.     

基于响应面分析法土壤种子库植被恢复的因素优化

表土厚度、覆盖物厚度、引用乔木种子数是土壤种子库应用于植被恢复工程中应考虑的重要因素.为了确定最优工程条件,利用Box-Behnken中心组合设计进行3因素3水平试验,用Design Expert进行响应面优化,以获取最优模型及各因素最优水平.结果表明: 本次响应面优化应采用二次模型,模型具有较好的统计学意义（P<0.0001）,能够很好地反映全体自变量和因变量的关系.响应模型的最优点为:表土厚度为4.3 cm,覆盖物厚度为2 cm,引入乔木种子数为224 ind·m^-2,种子库萌发个体总数可以高达6222 株·m^-2.土壤种子库幼苗萌发过程中,表土厚度与覆盖物厚度、表土厚度与引入乔木种子数交互作用显著,而覆盖物厚度与引入乔木种子数的交互作用不显著.表土厚度的响应曲线陡峭,且回归方程的标准化系数最大,是影响土壤种子库萌发物种个体总数的最重要因素.     

Synthesis of homo-N-nucleoside with 1,2,4-triazole-3-carboxamide

On the basis of potent biological activities of ribavirin and homo-N-nucleosides, a novel homo-N-1,2,4-triazole-3-carboxamide derivative 1 was synthesized starting from 2,3,5-tri-O-benzoylribofuranosyl-1-acetate as a potential antiviral agent.     

生态效率方法研究进展与应用

生态效率同时考虑经济效益和环境效益,是将可持续发展的宏观目标融入中观（区域）和微观（企业）的发展规划与管理中的有效工具。回顾了生态效率的概念和发展过程,分析了其内涵和指标体系,探讨了几种典型计算方法与模型,并介绍了国内外在企业、行业和区域3个层次上的应用实践,讨论和提出了进一步开展生态效率研究的焦点问题和未来方向。     

Biodegradation of p-nitrophenol via 1,2,4-benzenetriol by an Arthrobacter sp.

The degradation of p-nitrophenol (PNP) by Moraxella and Pseudomonas spp. involves an initial monooxygenase-catalyzed removal of the nitro group. The resultant hydroquinone is subject to ring fission catalyzed by a dioxygenase enzyme. We have isolated a strain of an Arthrobacter sp., JS443, capable of degrading PNP with stoichiometric release of nitrite. During induction of the enzymes required for growth on PNP, 1,2,4-benzenetriol was identified as an intermediate by gas chromatography-mass spectroscopy (GC-MS) and radiotracer studies. 1,2,4-Benzenetriol was converted to maleylacetic acid, which was further degraded by the beta-ketoadipate pathway. Conversion of PNP to 1,2,4-benzenetriol is catalyzed by a monooxygenase system in strain JS443 through the formation of 4-nitrocatechol, 4-nitroresorcinol, or both. Our results clearly indicate the existence of an alternative pathway for the biodegradation of PNP.     

Synthesis and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles

A series of 3,5-disubstituted-1,2,4-oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Formation of 1,2,4-oxadiazole ring was accomplished by the reaction of amidoxime with carboxylic acids. The in vitro cytotoxic effects of 3,5-disubstituted-1,2,4-oxadiazoles have been demonstrated across a wide array of tumor cell types and a few compounds exhibited specificity towards pancreatic (3f, 3h, 3j, and 3k) and prostate (3n) cancer cells. Among the prepared 3,5-disubstituted-1,2,4-oxadiazoles, compound 3n is the most selective (>450-fold) and compound 3p is the most cytotoxic (10 nM) against prostate cancer cell lines.     

Synthesis and antimalarial activity of 6-cycloalkylvinyl substituted 1,2,4-trioxanes

6-Cycloalkylvinyl substituted 1,2,4-trioxanes 6-15 have been prepared and tested against multi-drug resistant Plasmodium yoelii in mice. The most active trioxane 11 provides 80% protection to the treated mice. Further derivatization of 11 leads to decrease in antimalarial activity.     

Synthesis of Alkylating 1-Glycosyl-5-substituted 1,2,4-Triazoles1

Abstract

A series of alkylating derivatives of 5-subs-tituted 1-glycosyl-1,2,4-triazole having cytostatic activity has been prepared. The compounds synthesized include the 5-hydroxymethyl, 5-halomethyl, 5-(1-aziridino) methyl, and 5-bis (2-chloroethyl) aminomethyl derivatives.     

Synthesis of 1,2,4-triazole C-nucleosides from hydrazonyl chlorides and nitriles

A series of 1,3-diaryl-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1H-1,2,4-triazole nucleosides (3a-f) were synthesized via the intermolecular cyclization of hydrazonyl chlorides with peracylated ribofuranosyl cyanide catalyzed by Yb(OTf)3 or AgNO3, respectively. Similarly, the 1,2,4-triazole of glucopyranosyl C-nucleosides 5a,b were prepared from the hydrazonyl chlorides and the nitrile 4. Alternatively, the 1,2,4-triazole N-nucleoside 8 was obtained from cyclization of the unsymmetrical bis[alpha-(4-methoxyphenyl)aminobenzylidene]-hydrazine with peracylated 1-amino-D-manno-pentitol.     

Synthesis,structure, and antifungal evaluation of some novel 1,2,4-triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4-thiadiazole analogs

Novel 1-[[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptoacetyl]-4-alkyl/aryl-3-thiosemicarbazides (5–12) were synthesized by the reaction of 4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-ylmercaptoacetylhydrazide (4) with substituted isothiocyanates. Cyclodehydration of thiosemicarbazides with concentrated sulfuric acid yielded 2-[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptomethyl-5-alkyl/arylamino-1,3, 4-thiadiazoles (13–17). The new compounds were evaluated for in vitro antifungal activity using the microdilution method. The tested compounds showed varying degrees of activity against Microsporum gypseum NCPF-580, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans ATCC 10231 (MIC 8–4 μg/mL).     

Synthesis and Biological Activities of New 1,2,4-Triazol-3-one Derivatives

New 2-phenacyl-1,2,4-triazol-3-ones were obtained by the reaction of 5-alkyl-1,2,4-triazol-3-ones with α-bromoacetophenone in an alkaline medium. Selective reduction of the side chain carbonyl group to hydroxy group was achieved with NaBH₄. The reaction of some compounds containing a phenolic hydroxyl with 4-toluenesulfonyl chloride or benzyl bromide in the presence of NaOH led to tosylated or benzylated derivatives. The tosylation or benzylation at the alcoholic hydroxyl was carried out in the presence of sodium metal. Some of the newly synthesized compounds revealed an antimicrobial activity; 6 of 14 new compounds that were studied by the National Cancer Institute were found to possess antitumor activity.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 4, 2005, pp. 430–440.Original Russian Text Copyright ¢ 2005 by N. Demirbas, A. Demirbas, Karaoglu.The text was submitted by the authors in English.     

Synthesis and antituberculosis activity of new 3-alkylsulfanyl-1,2,4-triazole derivatives

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new alkylsulfanyltriazoles were synthesized and evaluated for antituberculosis activity. The reaction of thienyl-2-acetic acid with thiocarbohydrazide gave the mercaptotriazoles (II). The 4-amino-5-(2-thienylmethyl)-3-[1-(2-thienyl)-3-aryl)propion-3-yl]sulfanyl-4H-1,2,4-triazole (III) derivatives were synthesized by reacting the mercaptotriazoles with chalcones (I). Antituberculosis activities of the synthesized compounds were determined by broth microdilution assay, the Microplate Alamar Blue Assay, in BACTEC12B medium and results were screened in-vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H₃₇Rv (ATCC 27294) at 6.25?μg/ml and the tested compounds showed considerable inhibition ranging from 58–84%.     

Synthesis and antituberculosis activity of new 3-alkylsulfanyl-1,2,4-triazole derivatives

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new alkylsulfanyltriazoles were synthesized and evaluated for antituberculosis activity. The reaction of thienyl-2-acetic acid with thiocarbohydrazide gave the mercaptotriazoles (II). The 4-amino-5-(2-thienylmethyl)-3-[1-(2-thienyl)-3-aryl) propion-3-yl] sulfanyl-4H-1,2,4-triazole (III) derivatives were synthesized by reacting the mercaptotriazoles with chalcones (I). Antituberculosis activities of the synthesized compounds were determined by broth microdilution assay, the Microplate Alamar Blue Assay, in BACTEC 12B medium and results were screened in-vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv (ATCC 27294) at 6.25 microg/ml and the tested compounds showed considerable inhibition ranging from 58-84%.     

Synthesis of oligoribonucleotides via ribonucleoside-H-phosphonates

The synthesis of oligoribonucleotides via 5'-O-dimethoxytrityl-2'-E-tetrahydropyranyl-N-acylribonucleoside 3'-H-phosphonates is described. With these synthones and pivaloyl chloride as condensing agent, the synthesis of CpC and GpA in solution and the polymer support synthesis of (Up)4U and (Up)5C in manual variant and at the automatic synthesizer "Victoria-4M" was performed. The obtained oligonucleotide-H-phosphonates were oxidized to phosphates both with usually employed aqueous iodine solution and with of CCl4-Et3N-H2O (the Todd-Atherton reaction).     

Synthesis of 1,2,4-triazole derivatives containing benzothiazoles as pharmacologically active molecule

In attempt to make significant pharmacologically active molecule, we report here the synthesis and in vitro antimicrobial and antitubercular activity of various series of 3-(3-pyridyl)-5-(4-nitrophenyl)-4-(N-substituted-1,3-benzothiazol-2-amino)-4H-1,2,4-triazole. The antimicrobial activity of title compounds were examined against two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and three fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus) using the broth microdilution method and antitubercular activity H(37)Rv using Lowenstein-Jensen agar method.