26028-65-9Relevant academic research and scientific papers
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.
Discovery of [1,2,4]triazole derivatives as new metallo-β-lactamase inhibitors
Yuan, Chen,Yan, Jie,Song, Chen,Yang, Fan,Li, Chao,Wang, Cheng,Su, Huiling,Chen, Wei,Wang, Lijiao,Wang, Zhouyu,Qian, Shan,Yang, Lingling
, (2020/01/11)
The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.
Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway
Xiao, Shengnan,Wang, Xude,Xu, Lei,Li, Tao,Cao, Jiaqing,Zhao, Yuqing
, (2020/07/23)
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.
Dammarane sapogenin derivative and preparation method and application thereof
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, (2020/10/04)
The invention belongs to the technical field of medicines, and relates to a dammarane sapogenin derivative and a preparation method and application thereof. A series of dammarane sapogenin derivativesare obtained by combining dammarane sapogenins from plants with different groups. Anticancer activity evaluation and anticancer activity mechanism research are carried out on the derivative, and results show that the prepared dammarane sapogenin derivative has a remarkable anticancer effect, has no toxic effect on normal cells and can be used for preparing drugs for treating cancers.
Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs
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
, p. 209 - 220 (2019/01/10)
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.
Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
, p. 200 - 209 (2017/07/13)
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.
Thiazole triazole-6-acetamide derivative and application
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Paragraph 0013, (2018/03/01)
The invention discloses a thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative as shown in formula I or a pharmaceutically acceptable hydrate and salt thereof. The derivative comprises a stereisomer or tautomer thereof; R1 in the formula I is hydrogen, methyl, halogen, hydroxy, methoxy group, acetyl, propionyl, nitro or alkoxy; R2 and R3 are independently selected from C1-C6 alkyl or R2 and R3 and nitrogen atoms connected with the R2 and R3 are formed into pyrryl, piperidyl, morpholinyl, N-methyl piperazine and N-phenylpiperazine. The thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative disclosed by the invention has an obvious restraining function to acetylcholin esterase and is used for enhancing the memory of the patients suffering from dementia and Alzheimer's disease. The invention also relates to a preparation method of the compound and application of the compound for preparing the drug for treating the senile dementia.
Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties
Wei, Zhi-Yu,Cui, Bai-Ri,Cui, Xun,Wu, Yan-Ling,Fu, Yang,Liu, Li-Ping,Piao, Hu-Ri
, p. 47 - 60 (2016/12/16)
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.
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.
