Abstract
We report here that pregnenolonyl-α-glucoside (2), a steryl glycoside synthesized directly from pregnenolone and glucose via a consecutive multienzyme-catalyzed process, exhibits marked dose-dependent cytotoxic activity against HT29, AGS, and ES-2 cells with IC50 values of 23.5 to 50.9 μM. An in vitro CYP17A1 binding pattern assay and protein-ligand docking model support that 2, like abiraterone, binds in the active site heme iron pocket of CYP17A1.
MeSH terms
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Androstenes / metabolism
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Androstenes / pharmacology
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Bacteria / enzymology
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Catalytic Domain
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Cell Line, Tumor
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Cytochrome P-450 Enzyme Inhibitors / chemistry
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Cytochrome P-450 Enzyme Inhibitors / metabolism
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Cytochrome P-450 Enzyme Inhibitors / pharmacology*
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Glucosides / chemical synthesis
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Glucosides / metabolism
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Glucosides / pharmacology*
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Glycosylation
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HEK293 Cells
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Humans
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Molecular Docking Simulation
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Pregnenolone / analogs & derivatives*
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Pregnenolone / metabolism
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Pregnenolone / pharmacology*
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Protein Binding
Substances
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Androstenes
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Antineoplastic Agents
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Cytochrome P-450 Enzyme Inhibitors
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Glucosides
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Pregnenolone
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abiraterone