13004-42-7Relevant articles and documents
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Wessely,Lechner
, p. 395,403 (1931)
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Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases
Vo, Chau D.,Shebert, Hanna L.,Zikovich, Shannon,Dryer, Rebecca A.,Huang, Tony P.,Moran, Lindsey J.,Cho, Juno,Wassarman, Douglas R.,Falahee, Bryn E.,Young, Peter D.,Gu, Garrick H.,Heinl, James F.,Hammond, John W.,Jackvony, Taylor N.,Frederick, Thomas E.,Blair, Jimmy A.
, p. 5235 - 5244 (2017/11/01)
To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.
7-Hydroxy-benzopyran-4-one derivatives: A novel pharmacophore of peroxisome proliferator-activated receptor α and -γ (PPARα and γ) dual agonists
Matin, Azadeh,Gavande, Navnath,Kim, Moon S.,Yang, Nancy X.,Salam, Noeris K.,Hanrahan, Jane R.,Roubin, Rebecca H.,Hibbs, David E.
experimental part, p. 6835 - 6850 (2010/04/04)
Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead PPAR ligands were identified from "natraceuticals" and synthetic analogues. In total, 77 molecules, including chalcones, flavones, flavanones, isoflavones, and pyrazole derivatives, were screened and structure-activity relationship studies of the dual agonists undertaken. Compounds 68, 70, 72, and 76 were identified as novel and potent dual PPARα and γ agonists. These novel molecules may have the potential to be the future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome. 2009 American Chemical Society.
