165806-94-0Relevant articles and documents
Synthesis, characterization and biological activity of bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complexes
Ausserer, Marjana,Baecker, Daniel,Gallati, Caroline M.,Goetzfried, Sina K.,Gust, Ronald,Hermann, Martin,Kircher, Brigitte,Plangger, Matthias,Sagasser, Jessica,Wurst, Klaus
supporting information, p. 5471 - 5481 (2020/05/13)
Bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complexes (8a-h) with methoxy, methyl and fluorine substituents at different positions of the 4-aryl ring were synthesized and characterized. The relevance of the 2-methoxypyridin-5-yl residue and the substituents at the 4-aryl ring with regard to the activity against a series of cell lines was determined. Particularly against the Cisplatin-resistant ovarian cancer cell line A2780cis, the most active bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complex8cwas more active than Auranofin. It also inhibited thioredoxin reductase more effectively and induced high amounts of reactive oxygen species in A2780cis cells. Furthermore, its influence on non-cancerous SV 80 lung fibroblasts was lower than that of Auranofin. This fact, together with a high accumulation rate in tumor cells, determined on the example of MCF-7 cells, makes this complex an interesting candidate for further extensive studies.
Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor
Divakaran, Anand,Talluri, Siva K.,Ayoub, Alex M.,Mishra, Neeraj K.,Cui, Huarui,Widen, John C.,Berndt, Norbert,Zhu, Jin-Yi,Carlson, Angela S.,Topczewski, Joseph J.,Schonbrunn, Ernst K.,Harki, Daniel A.,Pomerantz, William C. K.
, p. 9316 - 9334 (2018/10/24)
As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-?-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-κB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38α. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.
Novel substituted imidazole compounds
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, (2008/06/13)
Novel 1,4,5 substituted imidazole compounds and compositions for use in therapy as CSBP/p38 kinase inhibitors.
