- Synthesis, antifungal activity, 3d-qsar, and molecular docking study of novel menthol-derived 1,2,4-triazole-thioether compounds
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A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results reveal
- Duan, Wen-Gui,Huang, Mei,Li, Bao-Yu,Lin, Gui-Shan
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- A High-Throughput Glycosyltransferase Inhibition Assay for Identifying Molecules Targeting Fucosylation in Cancer Cell-Surface Modification
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In cancers, increased fucosylation (attachment of fucose sugar residues) on cell-surface glycans, resulting from the abnormal upregulation of the expression of specific fucosyltransferase enzymes (FUTs), is one of the most important types of glycan modifications associated with malignancy. Fucosylated glycans on cell surfaces are involved in a multitude of cellular interactions and signal regulation in normal biological processes, as well as in disease. For example, sialyl LewisX is a fucosylated cell-surface glycan that is abnormally abundant in some cancers where it has been implicated in facilitating metastasis, allowing circulating tumor cells to bind to the epithelial tissue within blood vessels and invade into secondary sites by taking advantage of glycan-mediated interactions. To identify inhibitors of FUT enzymes as potential cancer therapeutics, we have developed a novel high-throughput assay that makes use of a fluorogenically labeled oligosaccharide as a probe of fucosylation. This probe, which consists of a 4-methylumbelliferyl glycoside, is recognized and hydrolyzed by specific glycoside hydrolase enzymes to release fluorescent 4-methylumbelliferone, yet when the probe is fucosylated prior to treatment with the glycoside hydrolases, hydrolysis does not occur and no fluorescent signal is produced. We have demonstrated that this assay can be used to measure the inhibition of FUT enzymes by small molecules, because blocking fucosylation will allow glycosidase-catalyzed hydrolysis of the labeled oligosaccharide to produce a fluorescent signal. Employing this assay, we have screened a focused library of small molecules for inhibitors of a human FUT enzyme involved in the synthesis of sialyl LewisX and demonstrated that our approach can be used to identify potent FUT inhibitors from compound libraries in microtiter plate format.
- Zhang, Xiaohua,Chen, Fei,Petrella, Alessandro,Chacón-Huete, Franklin,Covone, Jason,Tsai, Teng-Wei,Yu, Ching-Ching,Forgione, Pat,Kwan, David H.
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p. 715 - 724
(2019/03/26)
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- Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and Their Trifluoromethyl Analogues as Highly Efficient Antitubercular Agents Inhibiting Decaprenylphosphoryl-β- d -ribofuranose 2′-Oxidase
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We report herein the discovery of 3,5-dinitrophenyl 1,2,4-triazoles with excellent and selective antimycobacterial activities against Mycobacterium tuberculosis strains, including clinically isolated multidrug-resistant strains. Thorough structure-activity relationship studies of 3,5-dinitrophenyl-containing 1,2,4-triazoles and their trifluoromethyl analogues revealed the key role of the position of the 3,5-dinitrophenyl fragment in the antitubercular efficiency. Among the prepared compounds, the highest in vitro antimycobacterial activities against M. tuberculosis H37Rv and against seven clinically isolated multidrug-resistant strains of M. tuberculosis were found with S-substituted 4-alkyl-5-(3,5-dinitrophenyl)-4H-1,2,4-triazole-3-thiols and their 3-nitro-5-(trifluoromethyl)phenyl analogues. The minimum inhibitory concentrations of these compounds reached 0.03 μM, which is superior to all the current first-line anti-tuberculosis drugs. Furthermore, almost all compounds with excellent antimycobacterial activities exhibited very low in vitro cytotoxicities against two proliferating mammalian cell lines. The docking study indicated that these compounds acted as the inhibitors of decaprenylphosphoryl-β-d-ribofuranose 2′-oxidase enzyme, which was experimentally confirmed by two independent radiolabeling experiments.
- Karabanovich, Galina,Du?ek, Jan,Savková, Karin,Pavli?, Oto,Pávková, Ivona,Korábe?ny, Jan,Ku?era, Tomá?,Ko?ová Vl?ková, Hana,Huszár, Stanislav,Konyariková, Zuzana,Kone?ná, Klára,Jand'Ourek, Ond?ej,Stola?íková, Ji?ina,Korduláková, Jana,Vávrová, Kate?ina,Pávek, Petr,Klime?ová, Věra,Hrabálek, Alexandr,Miku?ová, Katarína,Roh, Jaroslav
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p. 8115 - 8139
(2019/09/30)
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- Synthesis and characterisation of some coumarin-1,2,4-triazol-3-thioether hybrid molecules
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A new series of N′-{[(4-methyl/phenyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio]acetyl}-2-oxo-2H-chromene-3-carbohydrazides was synthesised via the reaction of 2-[(4-methyl/phenyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio]acetohydrazides and 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-ones in good yields.
- Yilmaz, Fatih,Mente?e, Emre
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- Synthesis and invitro Evaluation of West Nile Virus Protease Inhibitors Based on the 2-{6-[2-(5-Phenyl-4H-{1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide Scaffold
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In recent years, clinical symptoms resulting from West Nile virus (WNV) infection have worsened in severity, with an increased frequency in neuroinvasive diseases among the elderly. As there are presently no successful therapies against WNV for use in humans, continual efforts to develop new chemotherapeutics against this virus are highly desired. The viral NS2B-NS3 protease is a promising target for viral inhibition due to its importance in viral replication and its unique substrate preference. In this study, a WNV NS2B-NS3 protease inhibitor with a 2-{6-[2-(5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide scaffold was identified during screening. Optimization of this initial hit by synthesis and screening of a focused compound library with this scaffold led to the identification of a novel uncompetitive inhibitor (1a24, IC50=3.4±0.2μM) of the WNV NS2B-NS3 protease. Molecular docking of 1a24 into the WNV protease showed that the compound interferes with productive interactions of the NS2B cofactor with the NS3 protease and is an allosteric inhibitor of the WNV NS3 protease.
- Samanta, Sanjay,Lim, Ting Liang,Lam, Yulin
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supporting information
p. 994 - 1001
(2013/07/27)
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- 1,2,4-Triazolyl azabicyclo[3.1.0]hexanes: A new series of potent and selective dopamine D3 receptor antagonists
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The discovery of new highly potent and selective dopamine (DA) D 3 receptor antagonists has recently allowed the characterization of the DA D3 receptor in a range of preclinical animal models of drug addiction. A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes, members of which showed a high affinity and selectivity for the DA D3 receptor and excellent pharmacokinetic profiles, is reported here. Members of a group of derivatives from this series showed good oral bioavailability and brain penetration and very high in vitro affinity and selectivity for the DAD3 receptor, as well as high in vitro potency for antagonism at this receptor. Several members of this series also significantly attenuate the expression of conditioned place preference (CPP) to nicotine and cocaine. 2009 American Chemical Society.
- Micheli, Fabrizio,Arista, Luca,Bonanomi, Giorgio,Blaney, Frank E.,Braggio, Simone,Capelli, Anna Maria,Checchia, Anna,Damiani, Federica,Di-Fabio, Romano,Fontana, Stefano,Gentile, Gabriella,Griffante, Cristiana,Hamprecht, Dieter,Marchioro, Carla,Mugnaini, Manolo,Piner, Jacqui,Ratti, Emiliangelo,Tedesco, Giovanna,Tarsi, Luca,Terreni, Silvia,Worby, Angela,Ashby Jr., Charles R.,Heidbreder, Christian
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scheme or table
p. 374 - 391
(2010/05/19)
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- Synthesis and evaluation of novel N-substituted-6-methoxynaphthalene-2- carboxamides as potential chemosensitizing agents for cancer
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A novel class of molecules with structure N-[3-(heteroaryl)propyl]-6- methoxynaphthalene-2-carboxamides 8-13 were synthesized by condensing 6-methoxy-2-naphthoyl chloride 1 with 3-(heteroaryl)propyl amines 2-7. Compounds 8-12 were evaluated in vitro, in P388 murine lymphocytic leukemia cell line (P388) using SRB assay for cytotoxicity and in adriamycin resistant P388 murine lymphocytic leukemia cell line (P388/ADR) using MTT assay for resistant reversal activity. Compounds 8-12 were non-toxic at lower dose of 20 μg/ml, and effectively reversed adriamycin resistance. However, at higher doses (40, 80 μg/ml) they showed significant cytotxicity and hence reversal potency was not determined at these concentrations.
- Lokhande, Tushar Narendra,Viswanathan, Chelakara Lakshmann,Juvekar, Aarti Shashikant
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body text
p. 894 - 896
(2009/08/15)
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- A one-pot synthesis of 4,5-disubstituted-1,2,4-triazole-3-thiones on solid support under microwave irradiation
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4,5-Di-substituted-1,2,4-triazole-3-thiones (4a-f) have been prepared in one stage from the reaction of acid hydrazide 1 with alkyl or aryl isothiocyanate 2 in the presence of a KOH (10%) solution on the surface of silica gel as well as on the surface of montmorillonite K10 under microwave irradiation. These triazoles have also been prepared from the reaction of 4-substituted-1-aroyl thiosemicarbazides 3a-e, with a KOH (10%) solution on the surface of silica gel under microwave irradiation. Copyright Taylor & Francis Group, LLC.
- Rostamizadeh, Shahnaz,Mollahoseini, Kambiz,Moghadasi, Samar
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p. 1839 - 1845
(2007/10/03)
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- NEW COMPOUNDS
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The present invention relates to new compounds of formula I, (I) a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
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- Synthesis and structure-activity relationship of C-3 substituted triazolylthiomethyl cephems
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A series of C-3 substituted triazolylthiomethyl cephems with an aminothiazolemethoxyiminoacetamido side chain at C-7 were synthesized and tested for antimicrobial activity against clinically-relevant isolates. The compound with 3-pyridyl at C-5 and methyl at N-4 of the triazole moiety exhibited good antibacterial activity against both Gram-positive and Gram-negative bacteria, with the exception of pseudomonas spp against which none of the derivatives exhibited favorable activity.
- Singh,Fiakpui,Galpin,Stewart,Singh,Micetich
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p. 301 - 309
(2007/10/03)
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- 5-Aryl-3-(alkylthio)-4H-1,2,4-triazoles as selective antagonists of strychnine-induced convulsions and potential antispastic agents
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Selected examples from three series of isomeric (alkylthio)-1,2,4- triazoles were prepared and examined for anticonvulsant activity versus strychnine-, maximal-electroshock-, pentylenetetrazole-, and 3- mercaptopropionic-acid-induced seizures in mice. A n
- Kane,Staeger,Dalton,Miller,Dudley,Ogden,Kehne,Ketteler,McCloskey,Senyah,Chmielewski,Miller
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p. 125 - 132
(2007/10/02)
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- 3-aryl-5-alkylthio-4H-1,2,4-traizoles for treatment of hyperreflexia due to spinal trauma
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This invention relates to the use of 3-aryl-5-alkylthio-4H-1,2,4-triazoles and the corresponding alkylsulfinyl- and alkylsulfonyl-4H-1,2,4-triazoles in the treatment of patients suffering from chronic hyperreflexia due to spinal trauma.
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- 3-aryl-5-alkylthio-4H-1,2,4-triazoles
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This invention relates to novel sulfone and sulfoxide derivatives of 3-aryl-5-alkylthio-4H-1,2,4-triazoles and to the use of 3-aryl-5-alkylthio-, alkylsulfinyl- and alkylsulfonyl-4H-1,2,4-triazoles in the treatment of patients suffering from convulsant seizures.
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- 4-Aralkyl-5-substituted-1,2,4-triazole-5-thiols
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Compounds of formula (I) and pharmaceutically acceptable salts thereof are described in which, n is 0 to 5; X1 to X5 are any accessible combination of hydrogen, halogen, C1 6alkyl, C1 6alkoxy, cyano, nitro, SONH2, SO2NH2, SO2CH3, SO2CH2F, SO2CHF2, SO2CF3, CF3, CHO, OH, CH2OH, CO2H, or CO2CpH2p+1wherein p is 1 to 4; R1 is phenyl substituted by X1 to X5, C1 4alkyl, C3 6cycloalkyl, or an arylC1 4alkyl group substituted by X1 to X5; R2 is hydrogen, C1 4alkyl or (CH2)m-CO2R3; m is 0 to 5; and R3 is H or C1 4alkyl. These compounds are dopamine-β-hydroxylase inhibitors. Pharmaceutical compositions are described as are methods of use. Processes for the preparation of these compounds are described.
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- 2,4-Dihydro-3H-1,2,4-triazole-3-thiones as Potential Antidepressant Agents
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A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity.Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides.Several
- Kane, John M.,Dudley, Mark W.,Sorensen, Stephen M.,Miller, Francis P.
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p. 1253 - 1258
(2007/10/02)
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- Reactions of Sulfur Monochloride with some Aromatic Aldehyde Semicarbazones and Thiosemicarbazones: New Syntheses of Substituted 2,4-Dihydro-1,2,4-triazol-3-ones, 2,4-Dihydro-1,2,4-triazole-3-thiones and 2-Amino-1,3,4-oxadiazoles
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Treatment of various substituted semicarbazones of aromatic aldehydes with sulfur monochloride yields the corresponding substituted 2,4-dihydro-1,2,4-triazol-3-ones.With thiosemicarbazones, the products are derivatives either of the 2-amino-1,3,4-thiadiaz
- Milcent, Rene,Nguyen, Thu-Huong
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p. 881 - 883
(2007/10/02)
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