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Synthesis and biological evaluation of 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins as potent NADPH oxidase (NOX) inhibitors

Title
Synthesis and biological evaluation of 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins as potent NADPH oxidase (NOX) inhibitors
Authors
Bae, Yun SooChoi, SunPark, Jung JaeJoo, Jung HeeCui, MinghuaCho, HyunsungLee, Won JaeLee, Sang Hyup
Ewha Authors
배윤수최선주정희
SCOPUS Author ID
배윤수scopus; 최선scopus; 주정희scopusscopus
Issue Date
2016
Journal Title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN
0968-0896JCR Link1464-3391JCR Link
Citation
vol. 24, no. 18, pp. 4144 - 4151
Keywords
ThiohydantoinBenzylideneAluminum chlorideNADPH oxidase (NOX)
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
We report the synthesis of novel 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3, and their biological evaluation using NADPH oxidase (NOX) 1 and 4. Based on structural and pharmacophore analyses of known inhibitors such as hydroxypyrazole 2, we envisioned interesting 2-thiohydantoin compounds, 3-substituted 5-benzylidene-1-methyl-2-thiohydantoins 3 that would be expected to well match the structural features in 2. Efficient synthesis of eighteen target compounds 3 were achieved through the synthetic pathway of 4 -> 11 -> 3, established after consideration of several plausible synthetic pathways. The inhibitory activities of compounds 3 against NOX 1 and 4 were measured, with some of the target compounds showing similar or higher activities compared with reference 2; in particular, compounds 3bz, 3cz, and 3ez were found to be promising inhibitors of both NOX 1 and 4 with modest isozyme selectivities, which highlights the significance of the 2-thiohydantoin substructure for inhibition of NOX 1 and 4. This marks the first time these compounds have been applied to the inhibition of NOX enzymes. (C) 2016 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.bmc.2016.06.056
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자연과학대학 > 생명과학전공 > Journal papers
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