Structure–activity relationships of furazano[3,4- b ]pyrazines as mitochondrial uncouplers
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چکیده
منابع مشابه
Uncouplers of rat-liver mitochondrial oxidative phosphorylation.
1. The ability of a series of compounds to uncouple oxidative phosphorylation of rat-liver mitochondria has been investigated. 2. The compounds were: 2-amino-1,1,3-tricyanopropene; carbonyl cyanide phenylhydrazone and its m-chloro and p-trifluoromethoxy derivatives; 4,5,6,7-tetrachloro-, 5-chloro-4-nitro-, 5-nitro-and 4,5,6,7-tetrachloro-1-methyl-benzotriazole; 4-hydroxy-3,5-di-iodo-, 3,5-di-br...
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BACKGROUND Mitochondrial dysfunction participates in the progression of several pathologies. Although there is increasing evidence for a mitochondrial role in liver disease, little is known about its contribution to hepatic stellate cell (HSC) activation. In this study we investigated the role of mitochondrial activity through mild uncoupling during in vitro activation of HSCs. METHODS Cultur...
متن کاملBiological effects and structure-activity relationships of 1,2-dihydropyrido[3,4-b]pyrazines.
The effects of a number of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines) upon the proliferation and the mitotic index of cultured L1210 cells and upon the survival of mice bearing P388 leukemia were determined. The 1,2-dihydrostructure and amino groups or masked amino groups at positions 5 and 7 were necessary for activity, and various substituents at positions 2 and 3 had c...
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We have discovered that some weak uncouplers (typified by butylated hydroxytoluene) have a dynamic range of more than 10(6) in vitro: the concentration giving measurable uncoupling is less than one millionth of the concentration causing full uncoupling. They achieve this through a high-affinity interaction with the mitochondrial adenine nucleotide translocase that causes significant but limited...
متن کاملMitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated e...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2015
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2015.06.040