- Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
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Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
- Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
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- Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
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Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
- Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
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p. 200 - 209
(2017/07/13)
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- Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties
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In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22?±?0.36% at a concentration of 3?×?10?5?mol/L (metoprolol: ?9.74?±?0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K+ channel and L-type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.
- Wei, Zhi-Yu,Cui, Bai-Ri,Cui, Xun,Wu, Yan-Ling,Fu, Yang,Liu, Li-Ping,Piao, Hu-Ri
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- An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
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A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
- Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
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p. 968 - 981
(2016/10/31)
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- Synthesis, characterization, and anticancer studies of S and N alkyl piperazine-substituted positional isomers of 1,2,4-triazole derivatives
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A series of 3-[3-[4-(substituted)-1-cyclicamine] propyl]thio-5- substituted[1,2,4]triazoles (8a-m) and 2-[3-[4-(substituted)-1-cyclicamine] propyl]-5-(substituted)-2,4-dihydro-3H[1,2,4]triazole-3-thiones (9a-h) were synthesized with good yields starting from corresponding carboxylic acids using two different methods. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Six compounds had shown good anticancer activity. The triazole derivatives, 9d, 8j, and 8i were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinant of their biological activity. Springer Science+Business Media 2013.
- Murty,Ram, Kesur R.,Rao, B. Ramalingeswara,Rao, Rayudu Venkateswara,Katiki, Mohana Rao,Rao, Janapala Venkateswara,Pamanji,Velatooru
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p. 1661 - 1671
(2014/05/06)
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- Magnetically Recyclable Nano-Fe 2O 3-Catalyzed Chemoselective Synthesis and Antioxidant Activity of Diethyl (3-((5-Aryl-1 H-1,2,4-triazol-3-yl)thio)propyl) phosphonates
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An efficient, green, and chemoselective S-alkylation of 5-aryl-1H-1,2,4-triazole-3-thiones with diethyl (3-bromopropyl)phosphonate in water, catalyzed by nano-Fe2O3 under ligand-and base-free conditions, is reported. Clean reaction, less expensive catalyst, excellent yields, and easy workup are the advantages of the present method. The catalyst can be easily collected by a magnet and recycled without significant loss in catalytic activity. The newly synthesized compounds were screened for their antioxidant property by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. The majority of the compounds exhibited good antioxidant activity.
- Murty,Katiki, Mohana Rao,Rao, B. Ramalingeswara,Nanubolu, Jagadeesh Babu,Buddana, Sudheer Kumar,Prakasham
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p. 2724 - 2737
(2014/08/18)
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- Mild and convenient one-pot synthesis of 2-amino-1,3,4-oxadiazoles promoted by trimethylsilyl isothiocyanate (TMSNCS)
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A mild, convenient, and efficient one-pot synthesis of amino-1,3,4- oxadiazoles is described. In situ preparation of various thiosemicarbazides by the reaction of different carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS), followed by cyclodesulfurization of thiosemicarbazides under basic conditions in the presence of I2/KI resulted in 2-amino-1,3,4-oxadiazoles in high yields (79-94%).
- Guda, Dinneswara Reddy,Cho, Hyeon Mo,Lee, Myong Euy
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p. 7684 - 7687
(2013/07/11)
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- Trimethylsilyl isothiocyanate (TMSNCS): An efficient reagent for the one-pot synthesis of mercapto-1,2,4-triazoles
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A mild, convenient, and efficient one-pot synthesis of mercapto-1,2,4- triazoles is described. Various hydrazides efficiently reacted with trimethylsilyl isothiocyanate (TMSNCS) under basic condition to give mercapto-1,2,4-triazoles in high yields.
- Guda, Dinneswara Reddy,Wang, Tengjiao,Cho, Hyeon Mo,Lee, Myong Euy
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supporting information
p. 5238 - 5242
(2012/11/07)
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- Synthesis of new S-alkylated-3-mercapto-1,2,4-triazole derivatives bearing cyclic amine moiety as potent anticancer agents
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A series of 3-[3-[4-(Substituted)-1-cyclicamine]propyl]thio-5- substituted[1,2,4]triazoles (8a-j) were synthesized with good yields starting from corresponding carboxylic acids. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Three compounds had shown good anticancer activity. The triazole derivatives, 8i and 8j were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinants of their biological activity.
- Murty,Ram, Kesur R.,Rao, Rayudu Venkateswara,Yadav,Rao, Janapala Venkateswara,Pamanji,Velatooru
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p. 276 - 281
(2012/06/18)
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- Efficient synthesis of antifungal active 9-substituted-3-aryl-5H,13aH- quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in ionic liquids
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The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1, 2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 in ionic liquid as solvent under microwave heating as well as using oil-bath heating at 80 °C. The products are obtained in the good to moderate yields and in high purity. These compounds have been screened for antifungal activity. The screening data indicate that the compounds 8a, 8b, 8c and 8d show excellent activity against Aspergillus niger 1000 μg concentration and Pencillium notatum species at 500 μg as well as 1000 μg concentrations whereas, these compounds show good to moderate activity against Aspergillus flavus and Rhizopus species at both the concentrations. Moreover, ionic liquid is found to be recyclable for at least three consecutive runs what makes the process cost-effective and economic that lead to the area of Green Chemistry as recyclability is one of the most important feature of Green Chemistry.
- Gupta, Monika
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p. 4919 - 4923
(2011/09/16)
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- Mild and efficient method to obtain glycosyl sulfones of mercaptotriazole
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Thioglycosides of mercaptotriazoles in the piranose and furanose series were oxidized to sulfones by a mild and efficient oxidation method, using KMnO4/CuSO4 in acetonitrile. The structural assignement of the newly synthesized compou
- Lascu, Anca,Sisu, Ioana,Bercean, Vasile,Lupea, Alfa Xenia,Caproiud, Miron T.,Sisu, Eugen
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scheme or table
p. 205 - 210
(2011/08/05)
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- One-pot synthesis of antifungal active 9-substituted-3-aryl-5H,13aH- quinolino [3,2-/][1,2,4]triazolo [4,3-b] [1,2,4]triazepines
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The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1, 2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 using catalytic amount of p-TsOH and N,N-dimethylformamide as an energy transfer medium using microwave heating as well as solvent using oil-bath heating at 80°C affords novel 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4] triazepines. The products are obtained in good to moderate yields and are in a state of high purity.
- Gupta, Monika,Paul, Satya,Gupta, Rajive
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scheme or table
p. 475 - 481
(2010/10/03)
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- Synthesis and antibacterial activities of new S-glycosides bearing 1,2,4-triazole
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Several new 5-aryl-3-(β-D-glucopyranosylthio)-1,2,4-triazoles have been synthesized. The structures of these new compounds were confirmed by 1H NMR, 13C NMR and elemental analyses.The antibacterial activities of the compounds were also evaluated.
- Chao, Shu-Jun,Geng, Ming-Jiang,Wang, Ying-Ling
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scheme or table
p. 731 - 736
(2011/03/21)
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- Synthesis and antifungal activity of novel 3,6-diaryl-5H-[1,2,4]triazolo[4, 3-b][1,2,4]triazepines
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(Chemical Equation Presented) 5-Aryl-3,4-diamino-1,2,4-triazoles 5 on treatment with β-chlorocinnamaldehydes 7 in the presence of catalytic amount of p-TsOH and N,N-dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil-bath heating at 80°C affords novel 3,6-diaryl-5H-[1,2,4]triazolo[4,3-b]-1,2,4]triazepines 8. The structures of the synthesized compounds were established on the basis of 1H NMR, IR, mass spectral data and elemental analysis.
- Gupta, Monika
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p. 1023 - 1027
(2008/03/29)
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- Synthesis and evaluation of anti-inflammatory activity of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their Michael addition products
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Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (4-10) were obtained in a one step synthesis by heating 3-aryl-5-mercapto-1,2,4-triazoles (3a-d) with chloroacetic acid and appropriate aromatic aldehyde in acetic acid and acetic anhydride in the presence of anhydrous NaOAc. Michael type addition of cyclic secondary amines (N-methylpiperazine, piperidine) to 4-10 gave 2-phenyl-6- (α-aminoarylmethyl)thiazolo[3,2-b]-1,2,4-triazole-5-ols (4a-10b). The structures of the compounds were confirmed by spectral and elementary analysis. The compounds synthesized in previous and present studies were investigated for their anti-inflammatory activities.
- Tozkoparan, Birsen,Kilcigil, Guelguen Ayhan,Ertan, Rahmiye,Ertan, Mevluet,Kelicen, Pelin,Demirdamar, Ruemeysa
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p. 1006 - 1011
(2007/10/03)
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- Condensed Tetrahydrobenzothiazoles: Part II- Synthesis of 2-Aryl-5,6,7,8-tetrahydro-s-triazolobenzothiazoles and 3-Aryl-5,6,7,8-tetrahydro-s-triazolobenzothiazoles
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Cyclization of 1-aroylthiosemicarbazides (I) under alkaline conditions gives 3-mercapto-5-aryl-s-triazoles (II), while their condensation with 2-chlorocyclohexanone (IIIa) furnishes 2-aroylhydrazino-4,5,6,7-tetrahydrobenzothiazoles (IV).The reaction of II with IIIa affords 2-aryl-5,6,7,8-tetrahydro-s-triazolobenzothiazoles (Va).Structure of Va has been established by comparison with isomeric 3-aryl-5,6,7,8-tetrahydro-s-triazolobenzothiazoles (VI), obtained by cyclization of IV.The reaction of 2-bromo-6-carbethoxycyclohexanone (IIIb) with II does not produce the expected 5-carbethoxy-2-aryl-5,6,7,8-tetrahydro-s-triazolo benzothiazoles (Vb), but gives Va.Hydrolysis and decarboxylation of Vb during the reaction to form Va are discussed.
- Balse, Mukta N.,Mahajanshetti, C. S.
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p. 260 - 262
(2007/10/02)
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