Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)
| Autor: | John M. Pezzuto, Eun-Jung Park, Abdelrahman S. Mayhoub, Mark Cushman, Tamara P. Kondratyuk, Laura Marler |
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| Rok vydání: | 2012 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Reductase Resveratrol Biochemistry Article Mice Structure-Activity Relationship chemistry.chemical_compound Stilbenes Drug Discovery NAD(P)H Dehydrogenase (Quinone) Animals Humans Enzyme inducer Thiazole Molecular Biology biology Chemistry Macrophages Organic Chemistry Free radical scavenger Quinone Thiazoles HEK293 Cells Enzyme Induction biology.protein Molecular Medicine NAD+ kinase |
| Zdroj: | Bioorganic & Medicinal Chemistry. 20:7030-7039 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2012.10.006 |
| Popis: | NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believed that QR1 inducers can act as cancer chemopreventive agents. Resveratrol (1) is a naturally occurring stilbene derivative that requires a concentration of 21 μM to double QR1 activity (CD = 21 μM). The stilbene double bond of resveratrol was replaced with a thiadiazole ring and the phenols were eliminated to provide a more potent and selective derivative 2 (CD = 2.1 μM). Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to a highly potent and selective QR1 inducer 9o with a CD value of 0.087 μM. |
| Databáze: | OpenAIRE |
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