- 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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- Triazolylthioacetamide: A Valid Scaffold for the Development of New Delhi Metallo-β-Lactmase-1 (NDM-1) Inhibitors
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The metallo-β-lactamases (MβLs) cleave the β-lactam ring of β-lactam antibiotics, conferring resistance against these drugs to bacteria. Twenty-four triazolylthioacetamides were prepared and evaluated as inhibitors of representatives of the three subclasses of MβLs. All these compounds exhibited specific inhibitory activity against NDM-1 with an IC50 value range of 0.15-1.90 μM, but no activity against CcrA, ImiS, and L1 at inhibitor concentrations of up to 10 μM. Compounds 4d and 6c are partially mixed inhibitors with Ki values of 0.49 and 0.63 μM using cefazolin as the substrate. Structure-activity relationship studies reveal that replacement of hydrogen on the aromatic ring by chlorine, heteroatoms, or alkyl groups can affect bioactivity, while leaving the aromatic ring of the triazolylthiols unmodified maintains the inhibitory potency. Docking studies reveal that the typical potent inhibitors of NDM-1, 4d and 6c, form stable interactions in the active site of NDM-1, with the triazole bridging Zn1 and Zn2, and the amide interacting with Lys 211 (Lys224).
- Zhai, Le,Zhang, Yi-Lin,Kang, Joon S.,Oelschlaeger, Peter,Xiao, Lin,Nie, Sha-Sha,Yang, Ke-Wu
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- 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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- Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway
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In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 μM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.
- Xiao, Shengnan,Wang, Xude,Xu, Lei,Li, Tao,Cao, Jiaqing,Zhao, Yuqing
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- Design and development of 1,3,5-triazine-thiadiazole hybrids as potent adenosine A2A receptor (A2AR) antagonist for benefit in Parkinson's disease
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Various studies showed adenosine A2A receptors (A2ARs) antagonists have profound therapeutic efficacy in Parkinsons Disease (PD) by improving dopamine transmission, thus being active in reversing motor deficits and extrapyramidal symptoms related to the disease. Therefore, in the presents study, we have showed the development of novel 1,3,5-triazine-thiadiazole derivative as potent A2ARs antagonist. In the radioligand binding assay, these molecules showed excellent binding affinity with A2AR compared to A1R, with significant selectivity. Results suggest, compound 7e as most potent antagonist of A2AR among the tested series. In docking analysis with A2AR protein model, compound 7e found to be deeply buried into the cavity of receptor lined via making numerous interatomic contacts with His264, Tyr271, His278, Glu169, Ala63, Val84, Ile274, Met270, Phe169. Collectively, our study demonstrated 1,3,5-triazine-thiadiazole hybrid as a highly effective scaffold for the design of new A2A antagonists.
- Agnihotri, Amol Kumar,Bhat, Hans Raj,Giri, Sabeena,Masih, Anup,Pandey, Nidhi,Shrivastava, Jitendra Kumar,Singh, Saumya,Singh, Udaya Pratap
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- Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs
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Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a–3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a–3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a–4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b–4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11–163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.
- Shahzad, Sohail Anjum,Yar, Muhammad,Khan, Zulfiqar Ali,Shahzadi, Lubna,Naqvi, Syed Ali Raza,Mahmood, Adeem,Ullah, Sami,Shaikh, Ahson Jabbar,Sherazi, Tauqir Ali,Bale, Adebayo Tajudeen,Kuku?owicz, J?drzej,Bajda, Marek
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p. 209 - 220
(2019/01/10)
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- Efficient synthesis of novel conjugated 1,3,4-oxadiazole-peptides
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We were interested in the design and synthesis of novel bioisosteric analogues of leuprolide acetate containing the oxadiazole moiety at the C- or N-terminal of the peptide. An efficient approach for the synthesis of 2-amino-1,3,4-oxadiazoles through the reaction of hydrazide with ammonium thiocyanate and desulfurization reaction of the thiosemicarbazides using different coupling reagents was employed. These compounds are bioisosteres of the amide bond. Furthermore, the coupling of 2-amino-1,3,4-oxadiazoles at the C-terminal of leuprolide analogues was carried out, using a coupling reagent in the solution phase. On the other hand, the addition of a 2-amino-1,3,4-oxadiazole to the N-terminal of the peptide sequence was carried out through the reaction of the 2-amino-1,3,4-oxadiazole with succinic anhydride that led to the formation of a carboxylic acid moiety. Addition of the synthesized oxadiazole containing carboxylic acid to the peptide sequence was performed using a coupling reagent and on the surface of the resin. The synthesized peptides containing the oxadiazole moiety at the C- or N-terminal of the peptide sequence are peptidomimetics of leuprolide acetate. All of the synthesized peptides were purified using preparative HPLC and their structures were confirmed using HR-MS (ESI).
- Golmohammadi, Farhad,Balalaie, Saeed,Hamdan, Fatima,Maghari, Shokoofeh
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supporting information
p. 4344 - 4351
(2018/03/21)
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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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- Synthesis and antidepressant activity of di substituted-5-Aryl-1,2,4- triazoles
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A series of 5-Aryl-1H-1,2,4-triazole-3-thiol (3) were synthesized. Alkylation of thiol group with N,Ndimethyl/ diethyl/dicyclo hexyl-(2-chloro ethyl) amine gave compounds N,N-disubstituted-2-(5-Aryl-1H-1,2,4-triazol-3- ylthio)ethanamine (4). These compounds were characterized on the basis of IR, 1H NMR, Mass spectral data, and elemental analysis. The newly synthesized compounds were screened for their antidepressant activity by using tail suspension test in mice. Springer Science+Business Media, LLC 2011.
- Radhika,Venkatesham,Sarangapani, Manda
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p. 3509 - 3513
(2013/02/25)
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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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- Synthesis and evaluation of some 2-[(substituted) ethanoyl]amino- 5-aryl-1,3,4-thiadiazoles as diuretic agents
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Twelve 2-[(substituted)ethanoyl]amino-5-aryl-1,3,4-thiadiazoles were prepared by the reaction of 2-(chloro ethanoyl)amino-5-aryl-1,3,4- thiadiazoles and various secondary amines. These compounds were screened for diuretic activity. The compounds namely 4a1, 4b2 and 4c2 showed good diuretic activity comparable with the standard drug acetazolamide at a dose level of 100 mg/kg, orally in albino rats.
- Jain, Sanmati K.,Mishra, Pradeep
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experimental part
p. 1305 - 1308
(2011/12/21)
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- The synthesis, X-ray crystal structure and optical properties of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives
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A series of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives was synthesized by the reaction of 3-substituted-1H-1,2,4-triazole-5-thiol and chloroacetyl ferrocene in the presence of sodium hydride and potassium iodide at reflux. The structures of the new compounds were determined by IR and 1H NMR spectroscopy and HRMS. The structure of compound 5c was established by X-ray crystallography. UV-vis absorption and fluorescence spectra were recorded in ethanol and dichloromethane. The results showed that compounds 5a-g display similar absorptions ranging from 300 to 500 nm and maximal emission bands are about 566 nm. The intensity of fluorescence and maximal emission bands are dependent on the groups bonded to triazole rings.
- Liu, Wei-Yong,Xie, Yong-Sheng,Zhao, Bao-Xiang,Lian, Song,Lv, Hong-Shui,Gong, Zhong-Liang,Shin, Dong-Soo
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scheme or table
p. 531 - 536
(2010/08/07)
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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 anti-microbial activity evaluation of some new 1-benzoyl-isothiosemicarbazides
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The synthesis of some aroylisothiosemicarbazides was accomplished and their biological activity against bacteria, fungi, and mycobacteria was investigated. Different synthetic pathways were followed according to the kind of substituents that were introduced on both the aroyl ring and the sulfur atom. Anti-bacterial activity was measured against Staphylococcus aureus, S. epidermidis, Streptococcus agalactiae and S. faecalis, Escherichia coli, and Salmonella typhi, while antifungal activity was evaluated against C. albicans. Two species, Mycobacterium tuberculosis H37RV and Mycobacterium avium ATCC19421, were employed to evaluate antimycobacterial activity.
- Plumitallo,Cardia,Distinto,DeLogu,Maccioni
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p. 945 - 952
(2007/10/03)
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- Potential antibacterial agents part-V. Synthesis and structural characterization of some new 3-aryl 7H, 6-(aryl) 5H-1, 2, 4-triazolo [3, 4-b]-1, 3, 5-thiadiazines
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N-(Substituted benzoyl) thiosemicarbazides 11a-e were treated with sodium hydroxide solution to give 3-aryl-5-mercapto-4H-1,2,4-triazole 111a-e which were subjected to Mannich Reaction in presence of 2-OC2H5, 4-NO2 and 2-OCH3 substituted anilines to give 3-aryl 7H, 6-(aryl) 5H-1,2,4-triazolo [3,4-b]-1,3,5-thiadiazines IVa-h. The compounds, IVa-h were compared with oxytetracycline and ampiclox (standard antibiotics) for their antibacterial activity.
- Sarfraz, Tahira B.,Husain, Shaheen A.,Murtaza, Najma,Siddiqui, Bina S.
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p. 334 - 337
(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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