22397-48-4Relevant academic research and scientific papers
Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile
Abdelazeem, Ahmed H.,El-Saadi, Mohammed T.,Safi El-Din, Asmaa G.,Omar, Hany A.,El-Moghazy, Samir M.
, p. 665 - 676 (2017)
The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects. The new compounds were evaluated in vitro for their COXs inhibitory activity and in vivo for their anti-inflammatory and analgesic potentials. Four compounds; diphenylthiazole glycine derivatives (15a, 15b) and diphenylimidazolo acetic acid derivatives (19a, 19b), which possess carboxylic acid group exhibited significant activity and selectivity against COX-1 over COX-2. Of these compounds, (4,5-bis(4-methoxyphenyl)thiazol-2-yl)glycine 15b was the most potent compound against COX-1 with an inhibitory half maximal concentration (IC50) of 0.32 μM and a selectivity index (COX-2 IC50/COX-1 IC50) of 28.84. Furthermore, an ulcerogenicity study was performed where the tested compounds demonstrated a significant gastric tolerance. Interestingly, the most selective COX-1 inhibitor showed higher analgesic activity in vivo as expected compared to their moderate anti-inflammatory activity. This study underscores the need for further design and development of novel analgesic agents with low tendency to cause gastric damage based on improving their COX-1 affinity and selectivity profile.
Synthesis and in vitro anticancer activities of selenium N-heterocyclic carbene compounds
Huang, Sheng,Sheng, Xinyu,Bian, Mianli,Yang, Zhibin,Lu, Yunlong,Liu, Wukun
, p. 435 - 444 (2021/07/14)
Fourteen novel selenium N-heterocyclic carbene (Se-NHC) compounds derived from 4,5-diarylimidazole were designed, synthesized, and evaluated as antiproliferative agents. Most of them were more effective toward A2780 ovarian cancer cells than HepG2 hepatocellular carcinoma cells. Among them, the most active compound 2b was about fourfold more active than the positive control ebselen against A2780 cells. In addition, this compound displayed twofold higher cytotoxicity to A2780 cells than to IOSE80 normal ovarian epithelial cells. Further studies revealed that 2b could induce reactive oxygen species production, damage mitochondrial membrane potential, block the cells in the G0/G1 phase, and finally promote A2780 cell apoptosis.
Application of N-heterocyclic carbene selenium-gold compound in preparation of carbapenem-resistant acinetobacter baumannii drug
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Paragraph 0024; 0029-0031; 0033; 0038, (2021/07/21)
The invention discloses application of an N-heterocyclic carbene selenium-gold compound in preparation of a novel antibacterial drug resistant to carbapenem acinetobacter baumannii infection, and belongs to the technical field of drug preparation. According to the N-heterocyclic carbene selenium-gold compound, selenium-containing imidazole N-heterocyclic carbene selenium is used for replacing a thiosaccharide ligand in a gold nofen structure; the reaction activity of Au-Se in the N-heterocyclic carbene selenium-gold compound is higher than that of an Au-S bond, so that the Au-S bond in a Jinnofen structure can be prevented from being easily damaged by reducing mercaptan to a certain extent; and toxic and side effects are caused by metabolism before reaching a target spot. In-vitro antibacterial activity shows that IC50 of the compounds H7 and H8 in inhibition of carbapenem-resistant acinetobacter baumannii is 3.34 mu M and 4.67 mu M, MIC of the same are both 10 mu M, and MBC of the same are both 20 mu M. The animal in-vivo administration also shows a good anti-drug-resistant bacterium effect, which proves that the compound can significantly prolong the survival time of mice infected by drug-resistant bacteria, and has important practical application value.
Specific group modified N1 and N3 substituted 4,5-diaryl imidazole ring carbine rhodium complex and preparation method and application thereof
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Paragraph 0120-0122, (2019/12/25)
The invention discloses a specific group modified N1 and N3 substituted 4,5-diaryl imidazole ring carbine rhodium complex and a preparation method and application thereof. The structure of the rhodiumcomplex is shown as the formula II (please see the specification for the formula II), wherein R1 is selected from halogen, and C1-4 alkoxy or aryl, R2 is selected from C1-4 alkyl, and substituted ornon-substituted C1-4 alkyl, and a substituent group is selected from an aromatic ring or C3-6 cycloalkyl. In-vivo experiments show that the tumor growth inhibition rate of the rhodium complex under the dosage of 10 mg.kg can reach 45%, and the rhodium complex has the very high tumor growth inhibition capability and high safety, and has good application prospects in the aspect of developing novel non-platinum efficient anticancer drugs.
A new rhodium(I) NHC complex inhibits TrxR: In vitro cytotoxicity and in vivo hepatocellular carcinoma suppression
Fan, Rong,Bian, Mianli,Hu, Lihong,Liu, Wukun
supporting information, (2019/10/01)
Thioredoxin reductase (TrxR) is often overexpressed in different types of cancer cells including hepatocellular carcinoma (HCC) cells and regarded as a target with great promise for anticancer drug research and development. Here, we have synthesized and characterized nine new designed rhodium(I) N-heterocyclic carbene (NHC) complexes. All of them were effective towards cancer cells, especially complex 1e was more active than cisplatin and manifested strong antiproliferative activity against HCC cells. In vivo anticancer studies showed that 1e significantly repressed tumor growth in an HCC nude mouse model and ameliorated liver lesions in a chronic HCC model caused by CCl4. Notably, a mechanistic study revealed that 1e can strongly inhibit TrxR system both in vitro and in vivo. Furthermore, 1e promoted intracellular ROS accumulation, damaged mitochondrial membrane potential, promoted cancer cell apoptosis and blocked the cells in the G1 phase.
Investigation of synthesis and some properties of the copper complexes containing imidazole ligand
Erdem, Emin,Akarsu, Mehri,Kilin?arslan, Rafet,Kaya?il, Ismail,Kara, Izzet,S?yleyici, Sevil
, p. 55 - 64 (2016/07/15)
The copper(II) complexes bearing tetrasubstituted imidazole derivatives containing oxygen donor as ligands (L1-6) were synthesized and characterized by spectroscopic methods, magnetic measurements, elemental and thermogravimetric analyses. The
A three-way switchable process for suzuki cross-coupling, hydrodehalogenation, or an assisted tandem hydrodehalogenation and suzuki cross-coupling sequence
Sandtorv, Alexander H.,Bjorsvik, Hans-Rene
supporting information, p. 3231 - 3243 (2013/12/04)
A three-way switchable Pd-catalyzed and microwave assisted process appropriate for selective arylation or hydrodehalogenation of the imidazole backbone was discovered and entirely optimized. The "arylation switch position" was adapted and optimized for the synthesis of 4,5-diaryl-1H-imidazoles, while the "hydrodehalogenation switch position" was used for the preparation of 4(5)-iodo-1H-imidazole. The hydrodehalogenation and the cross-coupling reactions were also successfully combined in "the third switch position" that performs an assisted tandem reaction sequence that produced 4(5)-aryl-1H-imidazole. All of the three pathways produced their corresponding products in excellent yield. Copyright
Synthesis, antitumor, and antibacterial activity of Bis[4,5-diarylimidazol- 2-ylidene]methane derivatives
Liu, Wukun,Chen, Xiaohua,Gust, Ronald
scheme or table, p. 557 - 564 (2012/08/27)
Cationic [bis(1,3-diethyl-4,5-diarylimidazol-2-ylidene)]Au(I) bromide complexes have demonstrated considerable potential as new antitumor agents. In order to investigate whether the gold is crucial for the antitumor activity, the imidazole ligands were connected by a methylene bridge. Biological evaluation revealed that bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]methane compounds exhibited growth inhibition effects against mammary (MCF-7 and MDA-MB 231) and colon (HT-29) carcinoma cell lines. In comparison with gold complexes, the methylene derivatives showed drastically reduced cell growth inhibitory properties. However, the growth of bacteria was significantly inhibited by bis[1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]methane dibromide (4) and opens a new application of this compound type. To investigate whether the gold in cationic [bis(1,3-diethyl-4,5-diarylimidazol-2-ylidene)]Au(I) bromide complexes is crucial for their antitumor activity, the imidazole ligands were connected by a methylene bridge. In comparison with the gold complexes, the methylene derivatives showed drastically reduced cell growth inhibitory properties. However, the growth of bacteria was significantly inhibited by bis[1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]methane dibromide (4), opening a new application of this compound type. Copyright
Synthesis and biological studies of silver N-heterocyclic carbene complexes derived from 4,5-diarylimidazole
Liu, Wukun,Bensdorf, Kerstin,Hagenbach, Adelheid,Abram, Ulrich,Niu, Ben,Mariappan, Aruljothi,Gust, Ronald
experimental part, p. 5927 - 5934 (2012/01/02)
A novel class of silver N-heterocyclic carbene complexes (5a-f) were synthesized in high yield by reacting silver(I) oxide with 4,5-diarylimidazolium halides (4a-f). The complexes were characterized using NMR and IR spectroscopy. The structure was confirmed on the example of bromo[1,3-diethyl-4,5-bis(4- fluorophenyl)imidazol-2-ylidene]silver(I) (5c) by crystal structure analysis. The X-ray structure indicated a three-dimensional coordination polymer with a repeating unit consisting of a Ccarben-Ag2-Br 2-Ccarben cluster. Pharmacological investigations revealed that all silver complexes possessed growth inhibitory effects against breast cancer (MCF-7 and MDA-MB-231) as well as colon carcinoma (HT-29) cells. The most active compound 5c was slightly less active against MCF-7 cells, more active against MDA-MB-231 cells and comparable active as cisplatin against HT-29 cells. Further pharmacological investigations were performed with selected compounds on estrogen receptor (ER) binding, DNA intercalation, cyclooxygenase (COX) inhibition and antibacterial activity. The complexes were only marginally active at the DNA, ER and the COX enzymes, so these targets can be excluded to be involved in the mode of action. However, the growth of bacteria was significantly inhibited by 5c and 5f and opens a new application of this complex type.
NHC gold halide complexes derived from 4,5-diarylimidazoles: Synthesis, structural analysis, and pharmacological investigations as potential antitumor agents
Liu, Wukun,Bensdorf, Kerstin,Proetto, Maria,Abram, Ulrich,Hagenbach, Adelheid,Gust, Ronald
supporting information; experimental part, p. 8605 - 8615 (2012/02/03)
A series of novel neutral NHC gold halide complexes derived from 4,5-diarylimidazoles were synthesized, characterized, and analyzed for biological effects. High growth inhibitory effects in MCF-7 and MDA-MB 231 breast cancer as well as HT-29 colon cancer cell lines depended on the presence of the C4,C5-standing aromatic rings. Methoxy groups at these rings did not change the growth inhibitory properties, while F-substituents in the ortho-position (5d) increased the activity in MCF-7 and MDA-MB 231 cells. The substituents at the nitrogen atoms and the oxidation state of the metal play a subordinate role. The most active bromo[1,3-diethyl-4,5-bis(2-fluorophenyl)-1,3- dihydro-2H-imidazol-2-ylidene]gold(I) (5d) was distinctly more active than cisplatin. All complexes caused thioredoxin reductase (TrxR) inhibition (EC 50 = 374-1505 nM) distinctly lower than auranofin (EC50 = 18.6 nM) excluding this enzyme as main target. Because of the low nuclear content, a participation of DNA interaction on the mode of action is very unlikely. The missing ER binding and the missing correlation of growth inhibition and inactivation of COX enzymes exclude these targets, too. (Figure presented)
