37536-29-1Relevant articles and documents
Inhibition of mild steel corrosion in 5 % HCl solution by 5-(2-hydroxyphenyl)-1,2,4-triazole-3-thione
Ouici,Benali,Harek,Larabi,Hammouti,Guendouzi
, p. 2777 - 2793 (2013)
A new corrosion inhibitor, namely 5-(2-hydroxyphenyl)-1,2,4-triazole-3- thione (5-HTT), has been synthesized and its influence on corrosion inhibition of mild steel in 5 % HCl solution has been studied using weight loss method and electrochemical measurements. Potentiodynamic polarization measurements clearly reveal that the investigated inhibitor is of mixed type, and it inhibits the corrosion of the steel by blocking the active site of the metal. Changes in impedance parameters were indicative of adsorption of 5-HTT on the metal surface, leading to the formation of protective films. The degree of the surface coverage of the adsorbed inhibitors was determined by weight loss measurements, and it was found that the adsorption of these inhibitors on the mild steel surface obeys the Langmuir adsorption isotherm. The effect of the temperature on the corrosion behavior with addition of 5 × 10-4 M of the inhibitor was studied in the temperature range 30-60 °C. The reactivity of this compound was analyzed through theoretical calculations based on density functional theory to explain the different efficiency of these compounds as a corrosion inhibitor.
Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
, (2021/03/24)
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.
Halogen-substituted triazolethioacetamides as a potent skeleton for the development of metallo-β-lactamase inhibitors
Zhang, Yilin,Yan, Yong,Liang, Lufan,Jiefeng,Wang, Xuejun,Li, Li,Yang, Kewu
, (2019/04/03)
Metallo-β-lactamases (MβLs) are the target enzymes of β-lactam antibiotic resistance, and there are no effective inhibitors against MβLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MβLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032–15.64 μM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 μM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 μM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27μM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.
Antibacterial drug for targeted therapy of staphylococcal infection by synergizing with antibiotic as well as synthesis method and application of antibacterial drug
-
Paragraph 0020; 0022, (2018/12/05)
The invention designs and synthesizes a novel antibacterial drug ASC for staphylococcus aureus based on a beta-lactam ring of a parent nucleus structure of beta-lactam antibiotic molecules, wherein the ASC is an antibacterial reagent and is also a broad-spectrum inhibitor of beta-lactam antibiotic drug-resistant target protein metal beta-lactamase; the ASC can synergize with three kinds of 7 to 8antibiotics such as beta-lactams, aminoglycosides and tetracyclines to carry out targeted therapy on the staphylococcal infection. The vitality of the antibiotics is increased by 4 to 128 times by combining with 1 [mu]g/ml dosage of ASC.
Synthesis of N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazides as antidepressants
Chelamalla, Radhika,Akena, Venkatesham,Manda, Sarangapani
, p. 1359 - 1366 (2017/06/05)
Abstract: A series of N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide were synthesized. Condensation of aromatic aldehydes with 2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide gave corresponding N′ -arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide. Spectral and elemental analysis was used for structural elucidation of novel 1, 2, 4-triazole schiff bases. The newly synthesized compounds were screened for their antidepressant activity by using tail suspension test in mice. Compound 4l showed significant activity among the series. Graphical Abstract: A series of new N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio)acetohydrazide have been synthesized and characterized. The results revealed that compound 4l with bromo substitution exhibited promising antidepressant activity among the series. [InlineMediaObject not available: see fulltext.].
Design, synthesis and in silico studies of new 5-substituted-2-(2-(5-aryl-1H-1, 2, 4-triazole-3-ylthio) acetyl) hydrazine carbothioamide/ carbox-amides for anticonvulsant activity
Chelamalla, Radhika,Makula, Ajitha,Manda, Sarangapani
, p. 1155 - 1163 (2017/11/14)
Background: Research on the synthesis of anticonvulsants is still in progress as they produce adverse effects with lesser activity as well as the patients become resistant to drug therapy. 1,2,4-triazole scaffold is a resource for the synthesis of anticonvulsant agents having better pharmacological action. Virtual Screening plays an important role to achieve binding affinity, receptor and library pre-processing, docking, scoring and top scoring hits. Optimization of drug ADME parameters continues to play an important role to achieve proof of concept, and ultimately efficacy, safely in clinical trials to address unmet medical need. Objective: The aim was to design, synthesise and evaluate anticonvulsant activity of a series of 5-substituted-2-(2-(5-aryl-1H-1,2,4-triazole-3-ylthio)acetyl) hydrazine carbothioamide/ carboxamides along with their in silico properties. Methods: Derivatives of 5-substituted-2-(2-(5-phenyl-1H-1,2,4-triazol-3-ylthio)acetyl)hydrazine carboxamides/ carbothioamides were obtained by condensation of Ethyl-2-(5-aryl-1H-1,2,4-triazol-3-ylthio)acetates with thiosemicarbazide or semicarbazide. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against pentylenetetrazole-induced seizure (PTZ) against diazepam as reference standard. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions. Results: Among the target compounds, 3f exhibited lower activity with 50% protection. The compounds 3e and 3h showed good to moderate levels of anticonvulsant activity with 83.3% protection at 100 mg/kg. The compounds 3g and 3i showed most significant anticonvulsant activity with 100% protection at a dose of 30 mg/kg. In silico results also revealed that 3g and 3i have shown maximum binding affinity to GABA AT protein among the tested compounds. Conclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.
Synthesis and Biological Evaluation of Some Heterocyclic Compounds from Salicylic Acid Hydrazide
Sarshira,Hamada,Moghazi,Abdelrahman
, p. 1970 - 1982 (2016/11/23)
Different heterocyclic compounds were prepared starting from 2-hydroxy benzohydrazide; for example, cyclization of hydrazide hydrazone 3 derived from 2-hydroxybenzohydrazide 2 with acetic anhydride or concentrated sulfuric acid gave 1,3,4-oxadiazole derivatives 4–5. On the other hand, direct cyclization of 2-hydroxy benzohydrazide 2 with one carbon cyclizing agent gave a new derivative of 1,3,4-oxadiazole 7, 8, 9, 10, 11. Heating of hydrazide hydrazone 3 with thioglycolic acid in pyridine gave thiazolidinone 12. When 2-hydroxy benzohydrazide 2 reacted with aliphatic carboxylic acids such as formic acid or acetic acid, it gave the corresponding N-formyl or N-acetyl derivatives 6. Subsequent cyclization of 6 using phosphorous pentasulphide in pyridine gave 1,3,4-thiadiazoles 13. Cyclization of 2-hydroxy benzohydrazide with ethyl acetoacetate gives pyrazolone derivative 14. Finally, when an ethanolic solution of acid hydrazide 2 was treated with ammonium thiocyanate in 35% HCl, it gave the thiosemicarbazide 15. Subsequent treatment of 15 with concentrated sulfuric acid or 10% sodium hydroxide gave 5-amino-1,3,4-thiadiazole 16 and 1,2,4-triazole 17, respectively. The structures of all newly isolated compounds were confirmed using1H NMR, IR spectra, and elemental analyses. The antimicrobial activities for all isolated compounds were examined against different microorganisms.
Triazolylthioacetamide: A Valid Scaffold for the Development of New Delhi Metallo-β-Lactmase-1 (NDM-1) Inhibitors
Zhai, Le,Zhang, Yi-Lin,Kang, Joon S.,Oelschlaeger, Peter,Xiao, Lin,Nie, Sha-Sha,Yang, Ke-Wu
, p. 413 - 417 (2016/05/19)
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).
Diaryl-Substituted Azolylthioacetamides: Inhibitor Discovery of New Delhi Metallo-β-Lactamase-1 (NDM-1)
Zhang, Yi-Lin,Yang, Ke-Wu,Zhou, Ya-Jun,LaCuran, Alecander E.,Oelschlaeger, Peter,Crowder, Michael W.
, p. 2445 - 2448 (2015/08/24)
The emergence and spread of antibiotic-resistant pathogens is a global public health problem. Metallo-β-lactamases (MβLs) such as New Delhi MβL-1 (NDM-1) are principle contributors to the emergence of resistance because of their ability to hydrolyze almost all known β-lactam antibiotics including penicillins, cephalosporins, and carbapenems. A clinical inhibitor of MBLs has not yet been found. In this study we developed eighteen new diaryl-substituted azolylthioacetamides and found all of them to be inhibitors of the MβL L1 from Stenotrophomonas maltophilia (KiiiII ion(s) preferentially via the triazole moiety, while other moieties interact mostly with the conserved active site residues Lys224 (CcrA, NDM-1, and ImiS) or Ser221 (L1).
Synthesis and antidepressant activity of di substituted-5-Aryl-1,2,4- triazoles
Radhika,Venkatesham,Sarangapani, Manda
, p. 3509 - 3513 (2013/02/25)
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.
