66630-70-4Relevant articles and documents
[Re(η6-C6H5-benzimidazole)2]+ and Derivatives as Dye Mimics; Synthesis, UV Absorption Studies and DFT Calculations
Gotzmann, Carla,Blacque, Olivier,Fox, Thomas,Alberto, Roger
, p. 2493 - 2498 (2021)
Functionalizations of highly oxidation and hydrolysis stable mono-cationic rhenium bis-arene complexes [Re(η6-C6H6)2]+ are of great interest. We directly built up structural features of the well-known Hoechst Dye on the coordinated arenes as a model for prospective DNA minor groove binding studies. Extensions of the aromatic bis-arene unit with functionalized and derivatized benzimidazole moieties resulted in a deep orange colour of the complexes, showing UV/Vis absorption spectra with multiple transition maxima. These have been assigned with support of DFT calculations to gain information about their charge transfer natures. The different transitions of the complexes, which are either intra-ligand, ligand-to-ligand or metal-to-ligand charge transitions, were additionally compared and discussed with the spectra of the corresponding free ligands.
PIPERAZINE DERIVATIVES AS MAGL INHIBITORS
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, (2019/05/02)
The invention provides new heterocyclic compounds having general Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1, R2, X, Y1 and Y2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
Targeting Phosphopeptide Recognition by the Human BRCA1 Tandem BRCT Domain to Interrupt BRCA1-Dependent Signaling
Periasamy, Jayaprakash,Kurdekar, Vadiraj,Jasti, Subbarao,Nijaguna, Mamatha B.,Boggaram, Sanjana,Hurakadli, Manjunath A.,Raina, Dhruv,Kurup, Lokavya Meenakshi,Chintha, Chetan,Manjunath, Kavyashree,Goyal, Aneesh,Sadasivam, Gayathri,Bharatham, Kavitha,Padigaru, Muralidhara,Potluri, Vijay,Venkitaraman, Ashok R.
, p. 677 - 12,690 (2018/06/21)
Intracellular signals triggered by DNA breakage flow through proteins containing BRCT (BRCA1 C-terminal) domains. This family, comprising 23 conserved phosphopeptide-binding modules in man, is inaccessible to small-molecule chemical inhibitors. Here, we develop Bractoppin, a drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem (t)BRCT domain, which selectively inhibits substrate binding with nanomolar potency in vitro. Structure-activity exploration suggests that Bractoppin engages BRCA1 tBRCT residues recognizing pSer in the consensus motif, pSer-Pro-Thr-Phe, plus an abutting hydrophobic pocket that is distinct in structurally related BRCT domains, conferring selectivity. In cells, Bractoppin inhibits substrate recognition detected by F?rster resonance energy transfer, and diminishes BRCA1 recruitment to DNA breaks, in turn suppressing damage-induced G2 arrest and assembly of the recombinase, RAD51. But damage-induced MDC1 recruitment, single-stranded DNA (ssDNA) generation, and TOPBP1 recruitment remain unaffected. Thus, an inhibitor of phosphopeptide recognition selectively interrupts BRCA1 tBRCT-dependent signals evoked by DNA damage. Periasamy et al. report the development of Bractoppin, a drug-like inhibitor of phosphopeptide recognition by the BRCA1 tBRCT domain, opening avenues to block intracellular signaling via a family of related targets.
