1591-38-4Relevant articles and documents
Synthesis and Structure-Activity Relationship of Xenocoumacin 1 and Analogues as Inhibitors of Ribosomal Protein Synthesis
Zumbrunn, Cornelia,Krüsi, Daniela,Stamm, Christina,Caspers, Patrick,Ritz, Daniel,Rueedi, Georg
supporting information, p. 891 - 897 (2020/12/15)
Ribosomal protein synthesis is an important target in antibacterial drug discovery. Numerous natural products have served as starting points for the development of antibiotics. We report here the total synthesis of xenocoumacin 1, a natural product that binds to 16S ribosomal RNA at a highly conserved region, as well as analogues thereof. Preliminary structure–activity relationship studies were aimed at understanding and modulating the selectivity between eukaryotic and prokaryotic ribosomes. Modifications were mainly tolerated in the aromatic region. Whole-cell activity against Gram-negative bacteria is limited by efflux and penetration, as demonstrated in genetically modified strains of E. coli. Analogues with high selectivity for eukaryotic ribosomes were identified, but it was not possible to obtain inhibitors selective for bacterial protein synthesis. Achieving high selectivity (albeit not the desired one) was thus possible despite the high homology between eukaryotic and prokaryotic ribosomes in the binding region.
Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
supporting information, p. 1207 - 1213 (2019/03/29)
To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex
Sutherell, Charlotte L.,Tallant, Cynthia,Monteiro, Octovia P.,Yapp, Clarence,Fuchs, Julian E.,Fedorov, Oleg,Siejka, Paulina,Müller, Suzanne,Knapp, Stefan,Brenton, James D.,Brennan, Paul E.,Ley, Steven V.
supporting information, p. 5095 - 5101 (2016/06/13)
Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.
